HLA-DQA2 explained

HLA class II histocompatibility antigen, DQ(6) alpha chain is a protein that in humans is encoded by the HLA-DQA2 gene. Also known as HLA-DXA or DAAP-381D23.2, it is part of the human leukocyte antigen system.^[1]

The protein encoded by this gene is expressed, but unlike HLA-DQA1, it is apparently unable to heterodimerize with HLA class II beta chain paralogues.^[2] The low level of HLA-DQA2 expression is apparently due to impaired transcription factor binding to the HLA-DQA2 gene promoter.^[3]

COVID-19

Transcriptome analysis of blood immune cells and nasopharyngeal cells before elaborate infection of study participants revealed that heightened expression of HLA-DQA2 correlates to a significantly lower chance of COVID-19 successfully infecting the individual.^[4]

References

Further reading

• Marsh SG, Bodmer JG . HLA class II nucleotide sequences, 1992 . Tissue Antigens . 40 . 5 . 229–243 . November 1992 . 1362295 . 10.1111/j.1399-0039.1992.tb02050.x .
• Kenter M, Otting N, Anholts J, Leunissen J, Jonker M, Bontrop RE . Evolutionary relationships among the primate Mhc-DQA1 and DQA2 alleles . Immunogenetics . 36 . 2 . 71–78 . 1992 . 1612647 . 10.1007/BF00215282 . 43642526 .
• Piatier-Tonneau D, Gastinel LN, Amblard F, Wojcik M, Vaigot P, Auffray C . Interaction of CD4 with HLA class II antigens and HIV gp120 . Immunogenetics . 34 . 2 . 121–128 . 1991 . 1869305 . 10.1007/BF00211424 . 10116507 .
• Rosenstein Y, Burakoff SJ, Herrmann SH . HIV-gp120 can block CD4-class II MHC-mediated adhesion . Journal of Immunology . 144 . 2 . 526–531 . January 1990 . 1967269 . 10.4049/jimmunol.144.2.526 .
• Bowman MR, MacFerrin KD, Schreiber SL, Burakoff SJ . Identification and structural analysis of residues in the V1 region of CD4 involved in interaction with human immunodeficiency virus envelope glycoprotein gp120 and class II major histocompatibility complex molecules . Proceedings of the National Academy of Sciences of the United States of America . 87 . 22 . 9052–9056 . November 1990 . 1978941 . 55099 . 10.1073/pnas.87.22.9052 . free .
• Gyllensten UB, Erlich HA . Ancient roots for polymorphism at the HLA-DQ alpha locus in primates . Proceedings of the National Academy of Sciences of the United States of America . 86 . 24 . 9986–9990 . December 1989 . 2513578 . 298627 . 10.1073/pnas.86.24.9986 . free .
• Clayton LK, Sieh M, Pious DA, Reinherz EL . Identification of human CD4 residues affecting class II MHC versus HIV-1 gp120 binding . Nature . 339 . 6225 . 548–551 . June 1989 . 2543930 . 10.1038/339548a0 . 4246781 . free . 1989Natur.339..548C .
• Diamond DC, Sleckman BP, Gregory T, Lasky LA, Greenstein JL, Burakoff SJ . Inhibition of CD4+ T cell function by the HIV envelope protein, gp120 . Journal of Immunology . 141 . 11 . 3715–3717 . December 1988 . 2846691 . 10.4049/jimmunol.141.11.3715 .
• Jonsson AK, Hyldig-Nielsen JJ, Servenius B, Larhammar D, Andersson G, Jörgensen F, Peterson PA, Rask L . Class II genes of the human major histocompatibility complex. Comparisons of the DQ and DX alpha and beta genes . The Journal of Biological Chemistry . 262 . 18 . 8767–8777 . June 1987 . 3036828 . 10.1016/S0021-9258(18)47482-0 . free .
• Horn GT, Bugawan TL, Long CM, Manos MM, Erlich HA . Sequence analysis of HLA class II genes from insulin-dependent diabetic individuals . Human Immunology . 21 . 4 . 249–263 . April 1988 . 3372263 . 10.1016/0198-8859(88)90034-1 .
• Andrieu JM, Even P, Venet A . AIDS and related syndromes as a viral-induced autoimmune disease of the immune system: an anti-MHC II disorder. Therapeutic implications . AIDS Research . 2 . 3 . 163–174 . 1986 . 3489470 . 10.1089/aid.1.1986.2.163 .
• Auffray C, Lillie JW, Korman AJ, Boss JM, Fréchin N, Guillemot F, Cooper J, Mulligan RC, Strominger JL . Structure and expression of HLA-DQ alpha and -DX alpha genes: interallelic alternate splicing of the HLA-DQ alpha gene and functional splicing of the HLA-DQ alpha gene using a retroviral vector . Immunogenetics . 26 . 1–2 . 63–73 . 1987 . 3610256 . 10.1007/bf00345456 . 19758795 .
• Trowsdale J, Lee J, Carey J, Grosveld F, Bodmer J, Bodmer W . Sequences related to HLA-DR alpha chain on human chromosome 6: restriction enzyme polymorphism detected with DC alpha chain probes . Proceedings of the National Academy of Sciences of the United States of America . 80 . 7 . 1972–1976 . April 1983 . 6300884 . 393734 . 10.1073/pnas.80.7.1972 . free . 1983PNAS...80.1972T .
• Auffray C, Lillie JW, Arnot D, Grossberger D, Kappes D, Strominger JL . Isotypic and allotypic variation of human class II histocompatibility antigen alpha-chain genes . Nature . 308 . 5957 . 327–333 . 1984 . 6584734 . 10.1038/308327a0 . 4358124 . 1984Natur.308..327A .
• Houlgatte R, Scarmato P, el Marhomy S, Martin M, Ostankovitch M, Lafosse S, Vervisch A, Auffray C, Platier-Tonneau D . HLA class II antigens and the HIV envelope glycoprotein gp120 bind to the same face of CD4 . Journal of Immunology . 152 . 9 . 4475–4488 . May 1994 . 7512597 . 10.4049/jimmunol.152.9.4475 .
• Chirmule N, McCloskey TW, Hu R, Kalyanaraman VS, Pahwa S . HIV gp120 inhibits T cell activation by interfering with expression of costimulatory molecules CD40 ligand and CD80 (B71) . Journal of Immunology . 155 . 2 . 917–924 . July 1995 . 7541827 . 10.4049/jimmunol.155.2.917 .
• Rowell JF, Stanhope PE, Siliciano RF . Endocytosis of endogenously synthesized HIV-1 envelope protein. Mechanism and role in processing for association with class II MHC . Journal of Immunology . 155 . 1 . 473–488 . July 1995 . 7602119 . 10.4049/jimmunol.155.1.473 . 19994352 .
• Rudy G, Lew AM . Limited polymorphism of the HLA-DQA2 promoter and identification of a variant octamer . Human Immunology . 39 . 3 . 225–229 . March 1994 . 8026991 . 10.1016/0198-8859(94)90264-X .
• Chen YH, Böck G, Vornhagen R, Steindl F, Katinger H, Dierich MP . HIV-1 gp41 binding proteins and antibodies to gp41 could inhibit enhancement of human Raji cell MHC class I and II expression by gp41 . Molecular Immunology . 31 . 13 . 977–982 . September 1994 . 8084338 . 10.1016/0161-5890(94)90092-2 .
• Chirmule N, Wang XP, Hu R, Oyaizu N, Roifman C, Pahwa R, Kalyanaraman VS, Pahwa S . Envelope glycoproteins of HIV-1 interfere with T-cell-dependent B cell differentiation: role of CD4-MHC class II interaction in the effector phase of T cell help . Cellular Immunology . 155 . 1 . 169–182 . April 1994 . 8168144 . 10.1006/cimm.1994.1110 . free .

Notes and References

1. Web site: Entrez Gene: HLA-DQA2 major histocompatibility complex, class II, DQ alpha 2.
2. Rudy GB, Lew AM . The nonpolymorphic MHC class II isotype, HLA-DQA2, is expressed on the surface of B lymphoblastoid cells . Journal of Immunology . 158 . 5 . 2116–2125 . March 1997 . 9036956 . 10.4049/jimmunol.158.5.2116 .
3. Indovina P, Megiorni F, Fontemaggi G, Coni P, Mora B, Mazzilli MC . Absence of in vivo DNA-protein interactions in the DQA2 and DQB2 promoter regions . Human Immunology . 62 . 5 . 504–508 . May 2001 . 11334674 . 10.1016/S0198-8859(01)00236-1 .
4. Lindeboom RG, Worlock KB, Dratva LM, Yoshida M, Scobie D, Wagstaffe HR, Richardson L, Wilbrey-Clark A, Barnes JL, Kretschmer L, Polanski K, Allen-Hyttinen J, Mehta P, Sumanaweera D, Boccacino JM, Sungnak W, Elmentaite R, Huang N, Mamanova L, Kapuge R, Bolt L, Prigmore E, Killingley B, Kalinova M, Mayer M, Boyers A, Mann A, Swadling L, Woodall MN, Ellis S, Smith CM, Teixeira VH, Janes SM, Chambers RC, Haniffa M, Catchpole A, Heyderman R, Noursadeghi M, Chain B, Mayer A, Meyer KB, Chiu C, Nikolić MZ, Teichmann SA . Human SARS-CoV-2 challenge uncovers local and systemic response dynamics . Nature . 631 . 8019 . 189–198 . July 2024 . 38898278 . 11222146 . 10.1038/s41586-024-07575-x .