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move historical guide to HLA nomenclature to more general Human leukocyte antigen page
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A*30:Cw*03 : higher viral load in HIV<ref name = "HIV1_HLAI"/><br/>
A*30:Cw*03 : higher viral load in HIV<ref name = "HIV1_HLAI"/><br/>


==Historical Guide to Understanding Nomenclature==
{|style="margin-left:2em; border:1px #ccffdd solid; background:#ebffef" align="right"
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{|style="text-align:left; margin-left:1em; background:#ebffef"
|- align = "center"
| <div style="font-size:medium; line-height:120%;">'''Overview'''</div>
|-
| '''A simple list that grew'''
|-
| column width = "300px" | A list of a dozen antigens was subdivided according to patterns of 'exclusivity'; the first clearly identified were HL-A1, A2 and A3 (now HLA-A1, -A2, -A3).
|- valign="bottom"
| row height = "30px" | '''Identification of "Blank" antigens'''
|-
| column width = "300px" | The unidentified or "blank" antigens became known as in "W" antigens, such as W35 (later B35) into a list of ~150 [[serotype]]s covering 9 [[locus (genetics)|genetic loci]]
|- valign="bottom"
| row height = "30px"| '''Protein and Gene Sequencing'''
|-
| column width = "300px" | The need for more precise identifications led to a brief period of protein sequencing followed by gene sequencing and allele typing (using [[PCR]]). Thousands of alleles and proteins have been identified for these 9 genetic loci.
|- valign="bottom"
| row height = "50px"| '''Gene identification effort reveals evolutionary '''<br />'''importance'''
|-
| column width = "300px" | The HLA genes are the fastest changing known coding genes in humans. The HLA proteins have a high rate of selection for variation. Many of the sites revealed by allograft antibodies (serotypes) are involved in binding foreign peptides<br />
|-
|}
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The naming of HLA "[[antigen]]s" is deeply rooted in the discovery history of their [[serotype]]s and [[allele]]s. There is no doubt that, except to an experienced HLA geneticist or immunologist, HLA terminology is bewildering.

Perspective is important to an understanding this system. Clinically, the point was to explain illness for patients who were transplant recipients. From this perspective, the cause of rejections were found to be antigens. In the same way bacterial antigens can cause inflammatory response, HLA antigens from the donor of the organ caused an inflammatory response when placed in a recipient. This is called allograft (allo = different, graft(medical) = transplant a part of the body to compensate for a defect) rejection.

* [[Lymphoid tissue|Lymphoid]] "antigens" became an experimental [[artifact]] of medical techniques (i.e., of transplantation). Simply, as scientist became familiarity with the human immune system we learned in allograft rejection, the cause was antibody production to allotypic proteins in donor tissue.

* From a more modern perspective, HLA [[gene product]]s (i.e., antigen-presenting, [[cell-surface receptor]]s) did not evolve to be transplantation antigens, nor to interfere with transplantation, organ transplantation being unknown until 1960. The HLA genes are much older. Variation in HLA major antigens is the cause of transplant rejection, but variation at HLA is under preservative selection (Called heterozygous selection or [[balancing selection]]). Variation of HLA has led to an estimate that they are at least 60 million years in age for humans (DRB1).<ref name="pmid8533083">{{cite journal | author = Ayala FJ | title = The myth of Eve: molecular biology and human origins | journal = Science | volume = 270 | issue = 5244 | pages = 1930–6 | year = 1995 | pmid = 8533083 | doi = }}</ref> In humans, the number of HLA alleles is expanding, even with many genes, many more are still tolerable as immune presentation antigens.

The scientific problem has been to explain the natural function of a molecule, such as a self [[cell-surface antigen|cell-surface receptor]] involved in [[immunity]]. It also seeks to explain how variation developed (perhaps by evolutionary pressure), and how the genetic mechanisms works ([[dominance (genetics)|dominant]], [[codominant]], [[Dominant gene#Incomplete dominance|semidominant]], or [[recessive]]; [[purifying selection]] or [[balancing selection]]).

===Transplantation and transplant rejection===
[[Image:Alloreactive Antisera.PNG|frame|left|'''A simple example of HLA antigen causing rejection''' <br\> A1, A2, B7, B8 do not cause reaction because they are in both donor and recipient, DR2 and DR3 are found on lymphoid cells]]
In the early 1960s, some physicians began more aggressive attempts at [[organ transplantation]]. Knowing little about ''compatibility factors'', they attempted transplantation between humans and even between non-humans and humans. <ref name="pmid14081245">{{cite journal | author = REEMTSMA K, MCCRACKEN BH, SCHLEGEL JU, PEARL M | title = HETEROTRANSPLANTATION OF THE KIDNEY: TWO CLINICAL EXPERIENCES | journal = Science | volume = 143 | issue = | pages = 700–2 | year = 1964 | pmid = 14081245 | doi = }}</ref> [[Immunosuppressive drugs]] worked for a time, but transplanted organs would either always fail or the patients would die from infections. Patients received skin, [[white blood cell]] or kidney donations from other donors (called [[allograft]]s, meaning 'of different genetics' graft). If these [[allograft]]s were rejected, it was found that the 'rejection' response was accompanied by an [[antibody]] mediated [[agglutination]] of red blood cells (See figure).<ref name="pmid4866325">{{cite journal | author = Rapaport FT, Kano K, Milgrom F | title = Heterophile antibodies in human transplantation | journal = J. Clin. Invest. | volume = 47 | issue = 3 | pages = 633–42 | year = 1968 | pmid = 4866325 | doi = }}</ref> The search for these cell surface antigens began. The process by which antibodies reduced function several fold.
* [[Transplant rejection#Acute rejection|Acute rejection - Antibodies]] could attract lymphocytes and cause them to lyse cells via the immune system's [[classical complement pathway]]
* Antibodies could bind to and alter function (eg, flow of a fluid, or prevention of binding of ligands to receptors)
* [[Cytokine]] responses that cause systemic responses.
<br />
<br />

====Different antigens can be identified====
In the accompanying figure, two similar [[haplotype]]s (unknown to early clinicians) are identical, except for the one ''antigen'' in the top haplotype. The transplant may not be rejected, but if rejection does occur that ''[[antigen]]'' in the donor tissue may have induced the dominant allo-reactive antibody in the recipient.
<br />
<br />

====Assaying Antiserum====
[[Image:anti-HLA agglutinated RBC.PNG|frame|right|'''Agglutination of [[HLA-A3]] positive [[red blood cell]]s''' (RBCs) with anti-A3 alloreactive [[antisera]] containing Anti-A3 [[IgM]]]]
'''Hemagglutination assay'''. In generating an immune response to an antigen, the [[B-cell]]s go through a process of maturation, from surface IgM production, to serum IgM production, to maturation into a [[plasma cell]] producing IgG. Graft recipients who generate an immune response have both IgM and IgG. The IgM can be used directly in [[hemagglutination]] assays, depicted on the left. IgM has 10 antigen binding regions per molecule, allowing cross-linking of cells. An antiserum specific for HLA-A3 will then agglutinate HLA-A3 bearing red blood cells if the concentration of IgM in the antiserum is sufficiently high. Alternatively, a second antibody to the invariable (F<sub>c</sub>) region of the IgG can be used to cross-link antibodies on different cells, causing agglutination.

'''Complement fixation assay'''. The [[complement fixation test]] was modified to assay Antiserum mediated RBC lysis.

'''Chromium release assay'''. This assay measures the release of (biological) radioactive chromium from cells as a result of killer cell activity. These cells are attracted to class I antigens that either carry foreign antigens, or are foreign to the immune system.

<br />
<br />

====The role of haplotypes in identifying antigens====
{|style="margin-right:1em; border:1px #ccffdd solid; background:#ebffef; text-align:center;" align="left"
|-
| || colspan = "3" | '''Haplotype 1''' || colspan = "3" |'''Haplotype 2'''
|-
! width = "80" | || width = "20" | A || width = "20" |Cw || width = "20" |B || width = "20" |A || width = "20" |Cw || width = "20" |B
|-
|Donor || 1 || 7 || 8 || '''3''' || 7 || 7
|-
|Recipient|| 1 || 7 || 8 || '''2''' || 7 || 7
|-
|Alloreactivity|| || || || <font color = "red">'''3'''</font>||
||
|-
| colspan = "7" align="right"|<font color = "light green">.</font>
|-
|Donor || 1 || 7 || 8 || '''2''' || 7 || 8
|-
|Recipient|| 1 || 7 || 8 || '''3''' || 7 || 8
|-
|Alloreactivity|| || || || <font color = "red">'''2'''</font>|| ||
|-
| colspan = "7" align="right"|<font color = "light green">.</font>
|-
|Donor || 1 || 7 || 8 || '''9''' || 7 || 8
|-
|Recipient|| 1 || 7 || 8 || '''3''' || 7 || 8
|-
|Alloreactivity|| || || || <font color = "red">'''9'''</font>|| ||
|-
| colspan = "7" align="right"|<font color = "light green">.</font>
|-
|Donor || 3 || 7 || 7 || '''1''' || 7 || 8
|-
|Recipient|| 3 || 7 || 7 || '''2''' || 7 || 8
|-
|Alloreactivity|| || || || <font color = "red">'''1'''</font>|| ||
|-
|}

Each person has two HLA [[haplotype]]s genes, one from each parent. The haplotype frequencies in Europeans are in strong [[linkage disequilibrium]]. This means there are much higher frequencies of certain haplotypes relative to the expectation based on serotype (or [[allele]]) frequencies. This aided the discovery of HLA antigens, but was unknown to the pioneering researchers,.

In the table, on the right, a fortuitous transplant between two unrelated individual has resulted in an antiserum allo-reactive to a single antigen. This allows researchers to match at least one antigen. Donors with A3 can be distinguished from recipients that lack A3.

In the case of the 5th example, there are several combinations, for example A2-Cw7-B7/A1-Cw7-B8, A2-Cw7-B7/A2-, A10-Cw7-B8. Given the distribution of haplotype in European Americans it is possible to estimate the probability of a random appearance of a single allotypic antigen. The most readily detected antigens are A3, A2, A1, A9, A10, and A11. Thus, the order of the antigens detected is largely a function of haplotype frequencies that could be combined to expose single antigen specificity when the highest probability is multiple specificities. Very rare haplotype alleles in this population tend to have been identified much later, in other populations.

In the next stage researchers are capable of matching 3 alleles (unknown as the HLA-A) but not the B except through linkage with A.
Occasionally A recombined with another B and resulted in a B allele mismatch.

{|style="margin-left:1em; border:1px #ccffdd solid; background:#ebffef; align:center;" align="right"
|-
| || colspan = "3" | '''Haplotype 1''' || colspan = "3" |'''Haplotype 2'''
|-
| || width = "30" | A || width = "30" |Cw || width = "30" |B || width = "30" |A || width = "30" |Cw || width = "30" |B
|-
|Donor || 1 || 7 || 8 || 2 || 7 || 7
|-
|Recipient|| 1 || 7 || 8 || 2 || 7 || 8
|-
|Alloreactivity|| || || || ||
|| <font color = "red">7</font>
|-
| colspan = "7" align="right"|<font color = "light green">.</font>
|-
|Donor || 3 || 7 || 7 || 2 || 7 || 8
|-
|Recipient|| 3 || 7 || 7 || 2 || 7 || 7
|-
|Alloreactivity|| || || || ||
|| <font color = "red">8</font>
|-
|}

In this instance, the A1/A2, A2/A3, A1/A3 are matched, decreasing the probability of a rejection because many are linked to a given haplotype. Occasionally the 'recombinant' A2-Cw7-B8 will cause alloreactivity to B8 if it was in the donor, or B7 if in the recipient.

This linkage disequilibrium in Europeans explains why A1, A2, A3, "A7"[B7], and "A8"[B8] were identified first. It would have taken substantially longer to identify other alleles because frequencies were lower, and haplotypes that migrated into the European population had undergone equilibration or were from multiple sources.

This is the genetic background against which scientists tried to uncover and understand the histocompatibility antigens.

===A list of antigens created===
In the late 1960's, scientist began reacting [[serum|sera]] from patients with rejecting transplants to donor or 'third party' tissues. Their [[sera]] (the liquid part of the blood when blood clots) was sensitized to the cells from donors - it was ''alloreactive''. Serum is rich in antibodies and can react to specific, inoculated antigens, becoming an ''[[antiserum]]''. An alloreactive antiserum could have strong reaction with the cells from one person (e.g., the transplant donor), mild reaction to another's cells, and no reaction to a third's cells (e.g., a close relative). Likewise, a different alloreactive antiserum might not react with the first, show moderate reaction to a second, and strong reaction to the third person's cells.

As a result of this complex reactivity, scientists were able to identify 15 antigens. These were assigned, a simple number, from 1 to 15. At first these 15 antigens were called the Hu-1 antigens<ref name="pmid4887739">{{cite journal | author = Bach FH, Amos DB | title = Hu-1: Major histocompatibility locus in man | journal = Science | volume = 156 | issue = 781 | pages = 1506–8 | year = 1967 | pmid = 4887739 | doi = }}</ref> and tentatively tagged as gene products of the Human equivalent of the mouse histocompatibility locus (MHC). In 1968, it was discovered that matching these antigens between kidney donor and recipient improved the likelihood of kidney survival in the recipient.<ref name="pmid4876470">{{cite journal | author = Patel R, Mickey MR, Terasaki PI | title = Serotyping for homotransplantation. XVI. Analysis of kidney transplants from unrelated donors | journal = N. Engl. J. Med. | volume = 279 | issue = 10 | pages = 501–6 | year = 1968 | pmid = 4876470 | doi = }}</ref> The antigen list still exists, although it has been reorganized to fit what we have since learned about genetics, refined, and greatly expanded.

===Lymphocyte bearing antigens recognized===
[[Image:LAvsA4.PNG|left]]
As the study of these 'rejection' [[sera]] and "allo"-antigens progressed, certain patterns in the antibody recognition were recognized. The first major observation, in 1969, was that an allotypic antibodies to "4" ("Four") was only found on lymphocytes, while most of the antigens, termed "LA", recognized most cells in the body.<ref name="pmid5773111">{{cite journal | author = Mann DL, Rogentine GN, Fahey JL, Nathenson SG | title = Molecular heterogeneity of human lymphoid (HL-A) alloantigens | journal = Science | volume = 163 | issue = 874 | pages = 1460–2 | year = 1969 | pmid = 5773111 | doi = }}</ref>

This group "4" antigen on lymphocytes would expand into "4a", "4b" and so on, becoming the "D" series (HLA-D (Class II) antigens) DP, DQ, and DR. This is an interesting history in itself.

The Hu-1 antigens were renamed the Human-lymphoid (HL) allo-antigens (HL-As). Allo-antigen comes from the observation that a tolerated protein in the donor becomes antigenic in the recipient. This can be compared with an [[autoantigen]], in which a person develops antibodies to one or more of their own proteins. This also suggested the donor and recipient have a different genetic makeup for these antigens. The "LA" group thereafter was composed of HL-A1, A2, A3, A5, A6, A7, A8, A9, A10, A11, A12, A13, A14 and A15 until further divisions and renaming were necessary. Some of the antigens above, for example HL-A1, are similar to [[HLA-A1]], as they are the same serotype. Some of the above, like A5, are not mentioned within the last few years, as they have been renamed.

===Subclassification of lymphoid antigens===
[[Image:HL-Series A and B.PNG|right]]
A series of tests on cultured cells revealed that, within the "LA" group, a donor tissue might have some antigens but not others. For example, an antiserum may react with patterns (on a given tissue):

* A1, A2, A7, A12
* A1, A3, A7, A8
* A1, A11, A8, A5
* A1, A8
* A2, A3, A7, A12
* A2, A11, A
* A2, A7, A12
* A3, A11, A7, B5
* A3, A7
* A11, A5

But fail to react in the following patterns:

* A1, A2, A3, ...
* A1, A2, A11
* A2, A3, A11
* . . . A7, A8, A12

===The HLA serotype series===
====Series "A"====
{|style="margin-left:2em; border:1px #ccffdd solid; background:#ebffef" align="right"
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{|style="text-align:left; margin-left:1em; background:#ebffef"
|- align = "center"
| <div style="font-size:medium; line-height:120%;">'''Genetics of Serotyping'''</div>
|-
| '''Effects of intraseries exclusion'''
|-
| column width = "300px" | Once it was determined that a tissue with two antigens of a series (such as "A") excluded the possibility of a third antigen of the same series, HLA serotypes began to clarify the genetic alleles present in humans. HL-Series "A" antigens became the HLA-A locus gene products, but with exceptions. Some serotypes, such as HL-A1 were so homogeneous in nature that mistaking that serotyped allele (HLA-A*0101) for another allele was unlikely. <br />
|-
|'''Interpreting Serotypes as Alleles'''
|-
| column width = "300px" | HL-A1 antiserum reacts to [[HLA-A1]] [[gene product]], a cell surface antigen, the similar cell surface antigens are found on almost all cells in the body. The frequency of HLA-A1 alleles is: HLA-A1'''*0101'''- 17.3%, '''*0103'''- 0.016%. The frequency of *0101 is 1000 times more abundant than *0103, or 99.9% of the time you have identified the correct allele with the serotype. The false negative rate for [[HLA-A1#Serotype|HLA-A1 serotype]] is 1% and the giving the HLA-A1 serotyping a [[specificity (tests)|specificity]] of 98.9% for the A1*0101 allele.<br />
|-
|'''Increasing confidence of Interpretation'''
|-
| column width = "300px" | Sensitivity is lower, particularly in the study of non-caucasians as the HL-A1 can cross-react to similar sites on [[Genetic recombination|genetic recombinant]]s (most often [[gene conversion]]). Sensitivity can be improved by knowing the haplotype. In Europe, HLA-A1 is strongly linked to a 'chunk of chromosome' called a 'haplotype'. This haplotype, Super-B8, is A1-Cw7-B8-DR3-DQ2, about 2 million DNA codons (the [[nucleotide]] building blocks) long. This chunk has avoided recombination for 1000s of years. When the A1 serotype is found with B8 (ie, the 'old' HL-A8) serotype in Europe, there is an even greater chance the HL-A1 antiserum has detected the A1*0101 allele's gene product. <br />
|}
|}
If 2 members of the series (A1, 2, 3, 9, 10, 11) were typed, a reaction with a third member of the series to the donor was not observed. This 'exclusivity' identified series "A".<ref>Bach ML, Bach FH. ''The genetics of histocompatibility''.(1970) Hosp. Practice 5(8): 33-44</ref> One might notice the similarities of this numeric series with the [[Template:HLA-A serotypes|HLA-A series]], as series "A" antigens are the first six members of [[HLA-A]]. Inadvertently, the scientist had discovered an antibody set that recognized only [[gene product]]s from one locus,{{Gene|HLA-A}} the "antigens" being the gene products. The implication is that an alloreactive anti-sera can be a tool for genetic identification.

==== Series "B" ====
Not long after the series A antigens were separated from the (rapidly expanding) list of antigens, it was determined another group also could be separated along the same ''logical'' lines. This group included HL-A5, A7, A8, A12. This became the series "B".
Note the similarity of Series "B" to the first few members [[Template:HLA-B serotypes|HLA-B serotypes]]. The names of these antigens were necessarily changed to fit the new putative series they were assigned to. From HL-A# to HLA-B#. The problem was that the literature was using "A7" and would soon be using "B7" as short hand for [[HLA-B7]].

==== Pseudo-series "w" ====
Since it was now certain, by the early 1970s, that the "antigens" were encoded by different series, implicit loci, numeric lists became somewhat cumbersome. Many groups were discovering antigens. In these instances an antigen was assigned a temporary name, like "RoMa2" and after discussion, the next open numeric slot could be assigned, but not to an "A" or "B" series until proper testing had been done. To work around this problem a 'workshop' number "w#" was often assigned while testing continued to determined which series the antigen belonged to.

====Series "C"====
Before too long, a series "C" was uncovered. Series C has proved difficult to serotype, and the alleles in the series still carry the "w" tag signifying that status; in addition, it reminds us that Series C were not assigned names the same way as Series A and B, it has its own numeric list Cw1, Cw2, Cw3.

===[[Serotype]] group expansion and refinement===
By the mid 1970s, genetic research was finally beginning to make sense of the simple list of antigens, a new series "C" had been discovered and, in turn genetic research had determined the order of HLA-A, C, B and D encoding loci on the human [[chromosome 6|6]]p.<ref name="pmid136874">{{cite journal | author = Yunis EJ, Dupont B, Hansen J | title = Immunogenetic aspects of allotransplantation | journal = Adv. Exp. Med. Biol. | volume = 73 Pt B | issue = | pages = 231–51 | year = 1976 | pmid = 136874 | doi = }}</ref> With new series came new antigens; Cw1 and 2 were quickly populated, although Cw typing lagged. Almost half of the antigens could not be resolved by serotyping in the early 90's. Currently genetics defines 18 groups.

At this point, Dw was still being used to identify DR, DQ, and DP antigens. The ability to identify new antigens far exceeded the ability to characterize those new antigens.

As technology for transplantation was deployed around the world, it became clear that these antigens were far from a complete set, and in fact hardly useful in some areas of the world (eg, Africa, or those descended from Africans). Some serotyping antibodies proved to be poor, with broad specificities, and new serotypes were found that identified a smaller set of antigens more precisely. These broad antigen groups, like A9 and B5, were subdivided into "split" antigen groups, A23 & A24 and B51 & B52, respectively. As the HL-A serotyping developed, so did identification of new antigens.

===Genetic identification===
In the early 1980's, it was discovered that a restriction fragment segregates with individuals who bear the [[HLA-B8]] serotype. By 1990, it was discovered that a single amino acid sequence difference between HLA-B44 (B*4401 versus B*4402) could result in allograft rejection. This revelation appeared to make serotyping based matching strategies problematic if many such differences existed. In the case of B44, the antigen had already been split from the B12 broad antigen group. In 1983, the cDNA sequences of [[HLA-A3]] and [[HLA-Cw3|Cw3]]<ref name="pmid6609814">{{cite journal | author = Strachan T, Sodoyer R, Damotte M, Jordan BR | title = Complete nucleotide sequence of a functional class I HLA gene, HLA-A3: implications for the evolution of HLA genes | journal = EMBO J. | volume = 3 | issue = 4 | pages = 887–94 | year = 1984 | pmid = 6609814 | doi = }}</ref> All three sequences compared well with mouse MHC class I antigens. The Western European [[HLA-B7]] antigen had been sequenced (although the first sequence had errors and was replaced). In short order, many HLA class I alleles were sequenced
including 2 Cw1 alleles.<ref name="pmid3375250">{{cite journal | author = Parham P, Lomen CE, Lawlor DA, ''et al'' | title = Nature of polymorphism in HLA-A, -B, and -C molecules | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 85 | issue = 11 | pages = 4005–9 | year = 1988 | pmid = 3375250 | doi = }}</ref>

By 1990, the full complexity of the HLA class I antigens was beginning to be understood. At the time new serotypes were being determined, the problem with multiple alleles for each serotype was becoming apparent by nucleotide sequencing. [[RFLP]] analysis helped determine new alleles, but sequencing was more thorough. Throughout the 1990s, PCR kits, called SSP-PCR kits were developed that allowed, at least under optimal conditions, the purification of DNA, PCR and Agarose Gel identification of alleles within an 8 hour day. Alleles that could not be clearly identified by serotype and PCR could be sequenced, allowing for the refinement of new PCR kits.

Serotypes like B*4401, B*4402, B*4403, each abundant within those with B44 serotypes could be determined with unambiguous accuracy. The molecular genetics has advanced HLA technology markedly over serotyping technology, but serotyping still survives. Serotyping can help to reveal which primers for sequencing may best work for new sequences. Serotyping had identified the most similar antigens that now form the HLA subgroups.


==References==
==References==

Revision as of 01:20, 26 July 2008

Template:PBB

HLA-A a human leukocyte antigen belongs to the MHC class I heavy chain receptors. The HLA-A is a heterodimeric receptor consisting of an HLA-A mature gene product and β2-microglobulin. The mature A chain is anchored in the membrane. MHC Class I molecules, such as HLA-A, are expressed in nearly all cells, and present small peptides to the immune system which surveys for non-self peptides. As in most mammalian populations, MHC Class I molecules are extremely variable in their primary structure, and HLA-A is ranked among the genes in humans with the fastest evolving coding sequence. After typing millions of individuals, as of 10/15/2007 617 variant alleles have been identified, encoding for 486 protein isoforms.

Function

MHC Class I molecules present smaller peptides, generally 9mers but longer molecules are tolerated, to the immune system. Several target cells include CD8+ T-lymphocytes. In response to signalling these lymphocytes result in apototic cell death. This mechanism is the result of responses to viral infection or intracellular microbial infections in which, as a means of preventing propagation, affected cells are killed and the antigens are presented to the immune system for Class II presentation and antibody development. Over a short period of time antibodies develop that can neutralize the ability of viruses and invasive bacteria to invade cells.

Subpages for A serotypes
Serotypes of HLA-A gene products
Broad
antigens		 Split antigens
HLA-A1
HLA-A2
HLA-A3
HLA-A9 HLA-A23 HLA-A24
HLA-A10 HLA-A25 HLA-A26 HLA-A34
HLA-A43 HLA-A66
HLA-A11
HLA-A19 HLA-A29 HLA-A30 HLA-A31
HLA-A32 HLA-A33 HLA-A74
HLA-A28 HLA-A68 HLA-A69
HLA-A36
HLA-A80

Structure and Serology

The HLA-A chain forms a binding cleft much like the MHC Class II molecules, the sides of the cleft are composed of alpha helices, the base is beta sheet and one end the relative closure limits the optimal length of peptide.

To the right is a table of serotypes of HLA-A and there general relationships.




Nomenclature

HLA alleles[1] and specificity
. Some Allele groups have been updated with recent information from the IMGT/HLA Database

Explanation - within each allele group there are alleles that are recognized by the serological typing for that group (e.g. A24-serotype) some within the group may also recognize the broad antigen typing (A9, A10, A19, A28) or only the broad antigen typing, some by alternative serological within the group (e.g. A2403), and some by no serological method. Obviously some groups are more closely related than other groups, and this is often reflected in broad antigen reactivity.

Associated Diseases

HLA-A associated diseases
Assoc.
disease		 Serotypes
Ankylosing
spondylitis
factor		 A24
Diabetes, Type-I
(factor)		 A1 A24
Hemochromatosis
(lower CD8+ cells)		 A3
myasthenia gravis
factor		 A3 A24 A30
Leukemia, T-cell
Adult onset		 A26 A68
Multiple
Sclerosis		 A3
Papilloma
virus susept.		 A11
Spontaneous
abortion		 A2

Diseases by Haplotype

A*02:Cw*16 : higher viral load in HIV[2]
A*23:B*14 : higher viral load in HIV[2]
A*23:Cw*07 : higher viral load in HIV[2]
A*30:Cw*03 : higher viral load in HIV[2]


References

  1. ^ Marsh SG, Albert ED, Bodmer WF, Bontrop RE, Dupont B, Erlich HA, Geraghty DE, Hansen JA, Hurley CK, Mach B, Mayr WR, Parham P, Petersdorf EW, Sasazuki T, Schreuder GM, Strominger JL, Svejgaard A, Terasaki PI, and Trowsdale J. (2005). "Nomenclature for factors of the HLA System, 2004". Tissue antigens. 65: 301–369. doi:10.1111/j.1399-0039.2005.00379.x. PMID 15787720.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  2. ^ a b c d Noble J, Valdes A, Bugawan T, Apple R, Thomson G, Erlich H (2002). "The HLA class I A locus affects susceptibility to type 1 diabetes". Hum Immunol. 63 (8): 657–64. doi:10.1016/S0198-8859(02)00421-4. PMID 12121673.{{cite journal}}: CS1 maint: multiple names: authors list (link)

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