HLA-A*02 (A*02) is a
human leukocyte antigen
The human leukocyte antigen (HLA) system or complex is a complex of genes on chromosome 6 in humans which encode cell-surface proteins responsible for the regulation of the immune system. The HLA system is also known as the human version of th ...
serotype
A serotype or serovar is a distinct variation within a species of bacteria or virus or among immune cells of different individuals. These microorganisms, viruses, or cells are classified together based on their surface antigens, allowing the epi ...
within the
HLA-A
HLA-A is a group of human leukocyte antigens (HLA) that are encoded by the HLA-A locus, which is located at human chromosome 6p21.3. HLA is a major histocompatibility complex (MHC) antigen specific to humans. HLA-A is one of three major types of ...
serotype group. The serotype is determined by the antibody recognition of the α2 domain of the HLA-A α-chain. For A*02, the α chain is encoded by the HLA-A*02 gene and the β chain is encoded by the
B2M locus
Locus (plural loci) is Latin for "place". It may refer to:
Entertainment
* Locus (comics), a Marvel Comics mutant villainess, a member of the Mutant Liberation Front
* ''Locus'' (magazine), science fiction and fantasy magazine
** ''Locus Award' ...
.
In 2010 the World Health Organization Naming Committee for Factors of the HLA System revised the nomenclature for HLAs. Before this revision, HLA-A*02 was also referred to as HLA-A2, HLA-A02, and HLA-A*2.
HLA-A*02 is one particular class I
major histocompatibility complex
The major histocompatibility complex (MHC) is a large locus on vertebrate DNA containing a set of closely linked polymorphic genes that code for cell surface proteins essential for the adaptive immune system. These cell surface proteins are calle ...
(MHC) allele group at the
HLA-A
HLA-A is a group of human leukocyte antigens (HLA) that are encoded by the HLA-A locus, which is located at human chromosome 6p21.3. HLA is a major histocompatibility complex (MHC) antigen specific to humans. HLA-A is one of three major types of ...
locus. The A*02 allele group can code for many proteins; as of December 2013 there are 456 different HLA-A*02 proteins.
Serotyping can identify as far as HLA-A*02, which is typically enough to prevent transplant rejection (the original motivation for HLA identification). Genes can further be separated by genetic sequencing and analysis. HLAs can be identified with as many as nine numbers and a letter (ex. HLA-A*02:101:01:02N).
HLA-A*02 is globally common, but particular variants of the allele can be separated by geographic prominence.
Serotype
The serotyping for the most abundant A*02 alleles is good. For A*02:03, A*02:06, A*02:07 serotyping is borderline useful. There is a separate serotyping for A203 and A210. As of December 2013, there are 456 alleles identified (mostly by sequence homology) as being A2, of those 27 are nulls, and a large majority have unknown serotypes, although it is highly probable that they will all return A2 serotypes.
Disease associations
HLAs serve as the primary link between the immune system and interior of cells. Thus any alteration to the HLA that induces decreased binding to a certain peptide or increased binding to a certain peptide, is expressed as, respectively, increased susceptibility to disease or decreased susceptibility to disease. In other words, certain HLAs may be incapable of binding any of the short peptides produced by
proteolysis
Proteolysis is the breakdown of proteins into smaller polypeptides or amino acids. Uncatalysed, the hydrolysis of peptide bonds is extremely slow, taking hundreds of years. Proteolysis is typically catalysed by cellular enzymes called protease ...
of pathogenic proteins. If HLAs bind none of the peptides produced by a pathogen, then there is no way for the immune system to tell that a cell is infected. Thus the infection can proliferate largely unchecked. It works the other way too. Some HLAs bind pathogenic peptide fragments with very high affinity. This in essence "supercharges" their immune system in regards to that particular pathogen, allowing them to easily control an infection that might otherwise be devastating.
Spontaneous abortion
The HLA-A*02 antigen has been associated with spontaneous abortion in infertile couples. In essence, there are indicators, albeit from a small study comparing HLA expression in fertile and infertile couples, that HLA-A*02 may induce increased maternal immune response to the fetus. This immune response could be compared to an allergic reaction, and, if severe enough, induces abortion of the fetus.
Although this is a very interesting correlation, the study which first uncovered this link was quite small and more work needs to be done to verify this hypothesis.
Human immunodeficiency virus
HLA-A*02 appears to stimulate peripheral blood mononuclear cells in a manner that inhibits HIV replication. This could be the reason for a documented 9-fold reduced risk of HIV transmission to infants during childbirth.
HIV has evolved mechanisms to combat immune recognition. HIV produces a protein called
Nef that binds to the cytoplasmic tail of HLA-A and B and diverts it to the lysosomes for destruction. This prevents the HLAs from being expressed on the cell surface and then functioning properly.
In addition, there are several HLA-A*02 haplotypes that appear to contribute heavily to higher or lower viral loads in HIV patients. HLA-A*02-C*16 and HLA-A*02-B*45 have been shown to contribute to significantly increased viral loads (greater than 100,000 copies per milliliter).
In summation, HLA-A*02 appears to be somewhat less effective than other HLA-As at protecting against HIV infections.
Hodgkin lymphoma
HLA-A*02 has been linked with decreased risk of developing Epstein-Barr virus (EBV)-positive Hodgkin lymphoma(HL). Among patients with EBV+ HL, only 35.5% of people expressed HLA-A*02 compared to 50.9% in the EBV-HL group and 53% in the control group. This is a significant decrease and is almost certainly a result of the abnormally efficient binding of HLA-A*02 to peptides originating from EBV.
This high affinity increases the probability of CD8+ t-cell recognition of EBV peptides held by HLA-A*02 complexes. This, in turn, enhances the immune system's ability to control and clear the EBV, which decreases the change of developing Hodgkin Lymphoma as a result of the infection.
By haplotype
A*02:Cw*16 is associated with increased higher viral load in HIV
Alleles
A2-B haplotypes
A2-B7 (Node in Netherlands)
A2-B5
*A2-B51
*A2-B52
A2-B8
A2-B13
A2-B14
*A2-B64
*A2-B65
A2-B15
*A2-B62
*A2-B63
*A2-B70,71,75,76
*A2-B46 (Node in Southern China, may be most abundant haplotype)
A2-B16
*
A2-B44
*A2-B45
A2-B18
A2-B27
A2-B35
A2-B37
A2-B39 (Node in North American Amerinds)
A2-B40
*A2-B60
*A2-B61
A2-B46
A2-Cw5-B44
A2-Cw5-B44 is the multi-serotype designation for the haplotype HLA-A*02:01~C*05:01~B*4402, the class I portion, of an ancestral haplotype (A2~B44~
DR4~
DQ8). The full haplotype is (for relative distances) see
Human leukocyte antigen
The human leukocyte antigen (HLA) system or complex is a complex of genes on chromosome 6 in humans which encode cell-surface proteins responsible for the regulation of the immune system. The HLA system is also known as the human version of th ...
s:
A ~ C ~ B ~ DRB1 ~ DQA1 ~ DQB1
Another haplotype that is more common in Central Europe is the (A2-B44-DR7-DQ2)
A ~ C ~ B ~ DRB1 ~ DQA1 ~ DQB1
Over northwestern Europe A2-B44 shows a single common ancestor which contributed
the Cw5 allele to the haplotype. The haplotype appears to have been introduced early in European prehistoric period, frequencies of the haplotype generally correlate with A1-Cw7-B8 and A2-B7. The haplotype is considerably more equilibrated relative to A1-B8 and a possible reason is gene flow from iberia or the east with related haplotypes after initial migrations.
References
{{DEFAULTSORT:HLA-A02
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