HLA-C explained

HLA-C (Human Leukocyte Antigen-C) belongs to the MHC class I heavy chain receptors. The C receptor is a heterodimer consisting of a HLA-C mature gene product and β2-microglobulin. The mature C chain is anchored in the membrane. MHC Class I molecules, like HLA-C, are expressed in nearly all cells, and present small peptides to the immune system which surveys for non-self peptides.

HLA-C is a locus on chromosome 6, which encodes for many HLA-C alleles that are Class-I MHC receptors. HLA-C, localized proximal to the HLA-B locus, is located on the distal end of the HLA region. Most HLA-C:B haplotypes are in strong linkage disequilibrium and many are as ancient as the human species itself.

Disease associations

Cw1: multinodular goiters^[1]

C*16: B-cell chronic lymphocytic leukemia^[2]

Nomenclature

C*01

• Cw1 serotype: C*01:02 and C*01:09
• Cw11
• C*01:04 to *01:08

C*02

• Cw2 serotype: C*02:02 and *02:08
• C*02:03 to *02:07, and 02:09

C*03

• Cw9 serotype: C*03:03
• Cw10 serotype: C*03:02, *03:04, and *03:06
• Cw3 serotype: C*03:07
• C*03:05 and 03:08

C*04

• Cw4 serotype: C*0401, *0407, and *0410

C*05

• Cw5 serotype: C*05:01 and *05:02
• C*05:03 to *05:06 and *05:08 to *05:10

C*06

• Cw6 serotype: C*06:02 and *06:05
• C*06:03, *06:04 and *06:06 to *06:11

C*07

• Cw7 serotype: C*07:01 to *07:06, *07:12, *07:14, *07:16
• C*07:07 to *07:11, *07:13, *07:15, and *07:17 to *07:29

C*08

• Cw8 serotype: C*08:01, *08:02 and *08:03
• C*08:05 to *08:12

Others

• C*12:02 to *12:15
• C*14:02 to *14:05
• C*15:01 to *15:11
• C*16:01 to *16:06
• C*17:01 to *17:03
• C*18:01 and *18:02

Common haplotype

Cw4-B35 (Western Africa to Native Americans) Cw7-B7 (Western Eurasia, South Africa)Cw7-B8 (Western Eurasia)Cw1-B46 (China, Indochina)Cw5-B44 (Western Eurasia)

Interactions

HLA-C has been shown to interact with:

• KIR2DL1,^{[3] [4] [5] [6]}
• Leukocyte immunoglobulin-like receptor family:
  • particularly the activating receptor LILRA1
  • LILRA3^[7]

Further reading

• Geyer M, Fackler OT, Peterlin BM . Structure--function relationships in HIV-1 Nef. . EMBO Rep. . 2 . 7 . 580–5 . 2001 . 11463741 . 1083955 . 10.1093/embo-reports/kve141 .
• Greenway AL, Holloway G, McPhee DA, Ellis P, Cornall A, Lidman M . HIV-1 Nef control of cell signalling molecules: multiple strategies to promote virus replication. . J. Biosci. . 28 . 3 . 323–35 . 2004 . 12734410 . 10.1007/BF02970151 . 33749514 .
• Bénichou S, Benmerah A . [The HIV nef and the Kaposi-sarcoma-associated virus K3/K5 proteins: "parasites"of the endocytosis pathway] . Med Sci (Paris) . 19 . 1 . 100–6 . 2003 . 12836198 . 10.1051/medsci/2003191100 . free .
• Leavitt SA, SchOn A, Klein JC, Manjappara U, Chaiken IM, Freire E . Interactions of HIV-1 proteins gp120 and Nef with cellular partners define a novel allosteric paradigm. . Curr. Protein Pept. Sci. . 5 . 1 . 1–8 . 2004 . 14965316 . 10.2174/1389203043486955 .
• Tolstrup M, Ostergaard L, Laursen AL, Pedersen SF, Duch M . HIV/SIV escape from immune surveillance: focus on Nef. . Curr. HIV Res. . 2 . 2 . 141–51 . 2004 . 15078178 . 10.2174/1570162043484924 .
• Joseph AM, Kumar M, Mitra D . Nef: "necessary and enforcing factor" in HIV infection. . Curr. HIV Res. . 3 . 1 . 87–94 . 2005 . 15638726 . 10.2174/1570162052773013 .
• Anderson JL, Hope TJ . HIV accessory proteins and surviving the host cell. . Current HIV/AIDS Reports . 1 . 1 . 47–53 . 2005 . 16091223 . 10.1007/s11904-004-0007-x . 34731265 .

External links

• Molecular Anthropology Yahoo Group
• HLA Allele and Haplotype Frequency Database

Notes and References

1. Ríos A, Rodríguez JM, Moya MR, Galindo PJ, Canteras M, Alvarez MR, Parrilla P . Associations of HLA-C alleles with multinodular goiters: study in a population from southeastern Spain. . Arch Surg . 141 . 2 . 123–8 . 2006 . 16490887 . 10.1001/archsurg.141.2.123 . free .
2. Montes-Ares O, Moya-Quiles MR, Montes-Casado M, Guerra-Pérez N, Campillo JA, González C, López-Bermejo A, Tamayo M, Majado MJ, Parrado A, Muro M, Marín L, Alvarez-López MR . Human leucocyte antigen-C in B chronic lymphocytic leukaemia. . Br J Haematol . 135 . 4 . 517–9 . 2006 . 17054674 . 10.1111/j.1365-2141.2006.06334.x . 23018830 .
3. Boyson JE, Erskine R, Whitman MC, Chiu M, Lau JM, Koopman LA, Valter MM, Angelisova P, Horejsi V, Strominger JL . Disulfide bond-mediated dimerization of HLA-G on the cell surface . Proc. Natl. Acad. Sci. U.S.A. . 99 . 25 . 16180–5 . December 2002 . 12454284 . 138585 . 10.1073/pnas.212643199 . 2002PNAS...9916180B . free .
4. Baba E, Erskine R, Boyson JE, Cohen GB, Davis DM, Malik P, Mandelboim O, Reyburn HT, Strominger JL . N-linked carbohydrate on human leukocyte antigen-C and recognition by natural killer cell inhibitory receptors . Hum. Immunol. . 61 . 12 . 1202–18 . December 2000 . 11163076 . 10.1016/s0198-8859(00)00184-1.
5. Valés-Gómez M, Reyburn HT, Mandelboim M, Strominger JL . Kinetics of interaction of HLA-C ligands with natural killer cell inhibitory receptors . Immunity . 9 . 3 . 337–44 . September 1998 . 9768753 . 10.1016/s1074-7613(00)80616-0. free .
6. Fan QR, Long EO, Wiley DC . Crystal structure of the human natural killer cell inhibitory receptor KIR2DL1-HLA-Cw4 complex . Nat. Immunol. . 2 . 5 . 452–60 . May 2001 . 11323700 . 10.1038/87766 . 24707532 .
7. Jones DC, Kosmoliaptsis V, Apps R, Lapaque N, Smith I, Kono A, Chang C, Boyle LH, Taylor CJ, Trowsdale J, Allen RL . HLA class I allelic sequence and conformation regulate leukocyte Ig-like receptor binding . J. Immunol. . 186 . 5 . 2990–7 . March 2011 . 21270408 . 10.4049/jimmunol.1003078 . free .