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. 1993 Dec 15;90(24):12005–12009. doi: 10.1073/pnas.90.24.12005

Allele-specific peptide ligand motifs of HLA-C molecules.

K Falk 1, O Rötzschke 1, B Grahovac 1, D Schendel 1, S Stevanović 1, V Gnau 1, G Jung 1, J L Strominger 1, H G Rammensee 1
PMCID: PMC48114  PMID: 8265661

Abstract

The consensus motifs of HLA-Cw3, -Cw4, -Cw6, and -Cw7 ligands were determined by pool sequencing. Together with information obtained by sequencing of some prominent individual peptides, the results indicate the following: (i) all four HLA-C molecules are associated with peptides. (ii) These peptides adhere to allele-specific motifs that are similar to those of to HLA-A or -B molecules; they have a preferred length of nine amino acids and an anchor residue at the C terminus. (iii) All four HLA-C molecules analyzed exhibit related peptide motifs, although each allelic product shows individual characteristics in fine specificity. (iv) Processing and origin of peptides appear not to be different from that of other class I molecules. (v) No obvious difference at C-terminal position 9 was present in the peptides isolated from the two dimorphic variants of HLA-C that determine dominant resistance to natural killer NK1-specific cells (HLA-Cw4, -Cw6) or to NK2-specific cells (HLA-Cw3, -Cw7) and that differ in two residues in or near the pocket at position 9.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Alexander J., Payne J. A., Shigekawa B., Frelinger J. A., Cresswell P. The transport of class I major histocompatibility complex antigens is determined by sequences in the alpha 1 and alpha 2 protein domains. Immunogenetics. 1990;31(3):169–178. doi: 10.1007/BF00211552. [DOI] [PubMed] [Google Scholar]
  2. Asahina A., Akazaki S., Nakagawa H., Kuwata S., Tokunaga K., Ishibashi Y., Juji T. Specific nucleotide sequence of HLA-C is strongly associated with psoriasis vulgaris. J Invest Dermatol. 1991 Aug;97(2):254–258. doi: 10.1111/1523-1747.ep12480361. [DOI] [PubMed] [Google Scholar]
  3. Bjorkman P. J., Saper M. A., Samraoui B., Bennett W. S., Strominger J. L., Wiley D. C. Structure of the human class I histocompatibility antigen, HLA-A2. Nature. 1987 Oct 8;329(6139):506–512. doi: 10.1038/329506a0. [DOI] [PubMed] [Google Scholar]
  4. Bodmer J. G., Marsh S. G., Albert E. D., Bodmer W. F., Dupont B., Erlich H. A., Mach B., Mayr W. R., Parham P., Sasazuki T. Nomenclature for factors of the HLA system, 1991. WHO Nomenclature Committee for factors of the HLA system. Tissue Antigens. 1992 Apr;39(4):161–173. doi: 10.1111/j.1399-0039.1992.tb01932.x. [DOI] [PubMed] [Google Scholar]
  5. Bonneville M., Moreau J. F., Blokland E., Pool J., Moisan J. P., Goulmy E., Soulillou J. P. T lymphocyte cloning from rejected human kidney allograft. Recognition repertoire of alloreactive T cell clones. J Immunol. 1988 Dec 15;141(12):4187–4195. [PubMed] [Google Scholar]
  6. Chen B. P., Lam V., Kraus E. E., DeMars R., Sondel P. M. Restriction of Epstein-Barr virus-specific cytotoxic T cells by HLA-A, -B, and -C molecules. Hum Immunol. 1989 Oct;26(2):137–147. doi: 10.1016/0198-8859(89)90099-2. [DOI] [PubMed] [Google Scholar]
  7. Colonna M., Spies T., Strominger J. L., Ciccone E., Moretta A., Moretta L., Pende D., Viale O. Alloantigen recognition by two human natural killer cell clones is associated with HLA-C or a closely linked gene. Proc Natl Acad Sci U S A. 1992 Sep 1;89(17):7983–7985. doi: 10.1073/pnas.89.17.7983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. D'Amaro J., Bach F. H., Van Rood J. J., Rimm A. A., Bortin M. M. HLA C associations with acute leukaemia. Lancet. 1984 Nov 24;2(8413):1176–1178. doi: 10.1016/s0140-6736(84)92741-7. [DOI] [PubMed] [Google Scholar]
  9. Dill O., Kievits F., Koch S., Ivanyi P., Hämmerling G. J. Immunological function of HLA-C antigens in HLA-Cw3 transgenic mice. Proc Natl Acad Sci U S A. 1988 Aug;85(15):5664–5668. doi: 10.1073/pnas.85.15.5664. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Duceman B. W., Ness D., Rende R., Chorney M. J., Srivastava R., Greenspan D. S., Pan J., Weissman S. M., Grumet F. C. HLA-JY328: mapping studies and expression of a polymorphic HLA class I gene. Immunogenetics. 1986;23(2):90–99. doi: 10.1007/BF00377967. [DOI] [PubMed] [Google Scholar]
  11. Falk K., Rötzschke O., Grahovac B., Schendel D., Stevanović S., Jung G., Rammensee H. G. Peptide motifs of HLA-B35 and -B37 molecules. Immunogenetics. 1993;38(2):161–162. doi: 10.1007/BF00190906. [DOI] [PubMed] [Google Scholar]
  12. Falk K., Rötzschke O., Rammensee H. G. Specificity of antigen processing for MHC class I restricted presentation is conserved between mouse and man. Eur J Immunol. 1992 May;22(5):1323–1326. doi: 10.1002/eji.1830220530. [DOI] [PubMed] [Google Scholar]
  13. Falk K., Rötzschke O., Stevanović S., Jung G., Rammensee H. G. Allele-specific motifs revealed by sequencing of self-peptides eluted from MHC molecules. Nature. 1991 May 23;351(6324):290–296. doi: 10.1038/351290a0. [DOI] [PubMed] [Google Scholar]
  14. Green J., Montasser M., Low H. C., Woodrow J. C. Investigation of the associations of a number of HLA antigens with psoriasis and psoriatic arthritis. Stat Med. 1988 Mar;7(3):443–450. doi: 10.1002/sim.4780070310. [DOI] [PubMed] [Google Scholar]
  15. Groop L., Koskimies S., Pelkonen R., Tolppanen E. M. Increased frequency of HLA-Cw4 in type 2 diabetes. Acta Endocrinol (Copenh) 1983 Dec;104(4):475–478. doi: 10.1530/acta.0.1040475. [DOI] [PubMed] [Google Scholar]
  16. Grunnet N., Kristensen T., Kissmeyer-Nielsen F. Cell mediated lympholysis in man. The impact of HLA-C antigens. Tissue Antigens. 1976 May;7(5):301–309. doi: 10.1111/j.1399-0039.1976.tb01071.x. [DOI] [PubMed] [Google Scholar]
  17. Guo H. C., Jardetzky T. S., Garrett T. P., Lane W. S., Strominger J. L., Wiley D. C. Different length peptides bind to HLA-Aw68 similarly at their ends but bulge out in the middle. Nature. 1992 Nov 26;360(6402):364–366. doi: 10.1038/360364a0. [DOI] [PubMed] [Google Scholar]
  18. Hill A. V., Elvin J., Willis A. C., Aidoo M., Allsopp C. E., Gotch F. M., Gao X. M., Takiguchi M., Greenwood B. M., Townsend A. R. Molecular analysis of the association of HLA-B53 and resistance to severe malaria. Nature. 1992 Dec 3;360(6403):434–439. doi: 10.1038/360434a0. [DOI] [PubMed] [Google Scholar]
  19. Jardetzky T. S., Lane W. S., Robinson R. A., Madden D. R., Wiley D. C. Identification of self peptides bound to purified HLA-B27. Nature. 1991 Sep 26;353(6342):326–329. doi: 10.1038/353326a0. [DOI] [PubMed] [Google Scholar]
  20. Kariyone A., Tanabe M., Juji T., Kano K., Takiguchi M. Functional expression of HLA-C blank antigens on human blood lymphocytes. J Immunol. 1990 Dec 1;145(11):3714–3718. [PubMed] [Google Scholar]
  21. Littaua R. A., Oldstone M. B., Takeda A., Debouck C., Wong J. T., Tuazon C. U., Moss B., Kievits F., Ennis F. A. An HLA-C-restricted CD8+ cytotoxic T-lymphocyte clone recognizes a highly conserved epitope on human immunodeficiency virus type 1 gag. J Virol. 1991 Aug;65(8):4051–4056. doi: 10.1128/jvi.65.8.4051-4056.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Ljunggren H. G., Kärre K. In search of the 'missing self': MHC molecules and NK cell recognition. Immunol Today. 1990 Jul;11(7):237–244. doi: 10.1016/0167-5699(90)90097-s. [DOI] [PubMed] [Google Scholar]
  23. Loveland B., Wang C. R., Yonekawa H., Hermel E., Lindahl K. F. Maternally transmitted histocompatibility antigen of mice: a hydrophobic peptide of a mitochondrially encoded protein. Cell. 1990 Mar 23;60(6):971–980. doi: 10.1016/0092-8674(90)90345-f. [DOI] [PubMed] [Google Scholar]
  24. Madden D. R., Gorga J. C., Strominger J. L., Wiley D. C. The structure of HLA-B27 reveals nonamer self-peptides bound in an extended conformation. Nature. 1991 Sep 26;353(6342):321–325. doi: 10.1038/353321a0. [DOI] [PubMed] [Google Scholar]
  25. Madden D. R., Gorga J. C., Strominger J. L., Wiley D. C. The three-dimensional structure of HLA-B27 at 2.1 A resolution suggests a general mechanism for tight peptide binding to MHC. Cell. 1992 Sep 18;70(6):1035–1048. doi: 10.1016/0092-8674(92)90252-8. [DOI] [PubMed] [Google Scholar]
  26. Malissen B., Kristensen T., Goridis C., Madsen M., Mawas C. Clones of human cytotoxic T lymphocytes derived from an allosensitized individual: HLA specificity and cell surface markers. Scand J Immunol. 1981 Sep;14(3):213–224. doi: 10.1111/j.1365-3083.1981.tb00558.x. [DOI] [PubMed] [Google Scholar]
  27. Maryanski J. L., Pala P., Corradin G., Jordan B. R., Cerottini J. C. H-2-restricted cytolytic T cells specific for HLA can recognize a synthetic HLA peptide. Nature. 1986 Dec 11;324(6097):578–579. doi: 10.1038/324578a0. [DOI] [PubMed] [Google Scholar]
  28. Müller C. A., Hasmann R., Grosse-Wilde H., Vögeler U., Bei-Jun C., Dopfer R., Waller H. D. Significant association of acute lymphoblastic leukemia with HLA-Cw7. Genet Epidemiol. 1988;5(6):453–461. doi: 10.1002/gepi.1370050609. [DOI] [PubMed] [Google Scholar]
  29. Ozawa A., Ohkido M., Inoko H., Ando A., Tsuji K. Specific restriction fragment length polymorphism on the HLA-C region and susceptibility to psoriasis vulgaris. J Invest Dermatol. 1988 Mar;90(3):402–405. doi: 10.1111/1523-1747.ep12456500. [DOI] [PubMed] [Google Scholar]
  30. Parham P., Brodsky F. M. Partial purification and some properties of BB7.2. A cytotoxic monoclonal antibody with specificity for HLA-A2 and a variant of HLA-A28. Hum Immunol. 1981 Dec;3(4):277–299. doi: 10.1016/0198-8859(81)90065-3. [DOI] [PubMed] [Google Scholar]
  31. Pohla H., Kuon W., Tabaczewski P., Doerner C., Weiss E. H. Allelic variation in HLA-B and HLA-C sequences and the evolution of the HLA-B alleles. Immunogenetics. 1989;29(5):297–307. doi: 10.1007/BF00352839. [DOI] [PubMed] [Google Scholar]
  32. Rammensee H. G., Falk K., Rötzschke O. Peptides naturally presented by MHC class I molecules. Annu Rev Immunol. 1993;11:213–244. doi: 10.1146/annurev.iy.11.040193.001241. [DOI] [PubMed] [Google Scholar]
  33. Rötzschke O., Falk K., Stevanović S., Grahovac B., Soloski M. J., Jung G., Rammensee H. G. Qa-2 molecules are peptide receptors of higher stringency than ordinary class I molecules. Nature. 1993 Feb 18;361(6413):642–644. doi: 10.1038/361642a0. [DOI] [PubMed] [Google Scholar]
  34. Saper M. A., Bjorkman P. J., Wiley D. C. Refined structure of the human histocompatibility antigen HLA-A2 at 2.6 A resolution. J Mol Biol. 1991 May 20;219(2):277–319. doi: 10.1016/0022-2836(91)90567-p. [DOI] [PubMed] [Google Scholar]
  35. Schendel D. J., Reinhardt C., Nelson P. J., Maget B., Pullen L., Bornkamm G. W., Steinle A. Cytotoxic T lymphocytes show HLA-C-restricted recognition of EBV-bearing cells and allorecognition of HLA class I molecules presenting self-peptides. J Immunol. 1992 Oct 1;149(7):2406–2414. [PubMed] [Google Scholar]
  36. Shawar S. M., Vyas J. M., Rodgers J. R., Cook R. G., Rich R. R. Specialized functions of major histocompatibility complex class I molecules. II. Hmt binds N-formylated peptides of mitochondrial and prokaryotic origin. J Exp Med. 1991 Oct 1;174(4):941–944. doi: 10.1084/jem.174.4.941. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Steinle A., Nössner E., Schendel D. J. Isolation and characterization of a genomic HLA-Cw6 clone. Tissue Antigens. 1992 Mar;39(3):134–137. doi: 10.1111/j.1399-0039.1992.tb01923.x. [DOI] [PubMed] [Google Scholar]
  38. Storkus W. J., Dawson J. R. Target structures involved in natural killing (NK): characteristics, distribution, and candidate molecules. Crit Rev Immunol. 1991;10(5):393–416. [PubMed] [Google Scholar]
  39. Storkus W. J., Salter R. D., Cresswell P., Dawson J. R. Peptide-induced modulation of target cell sensitivity to natural killing. J Immunol. 1992 Aug 15;149(4):1185–1190. [PubMed] [Google Scholar]
  40. Sutton J., Rowland-Jones S., Rosenberg W., Nixon D., Gotch F., Gao X. M., Murray N., Spoonas A., Driscoll P., Smith M. A sequence pattern for peptides presented to cytotoxic T lymphocytes by HLA B8 revealed by analysis of epitopes and eluted peptides. Eur J Immunol. 1993 Feb;23(2):447–453. doi: 10.1002/eji.1830230222. [DOI] [PubMed] [Google Scholar]
  41. Van Pel A., De Plaen E., Boon T. Selection of highly transfectable variant from mouse mastocytoma P815. Somat Cell Mol Genet. 1985 Sep;11(5):467–475. doi: 10.1007/BF01534840. [DOI] [PubMed] [Google Scholar]
  42. Zemmour J., Little A. M., Schendel D. J., Parham P. The HLA-A,B "negative" mutant cell line C1R expresses a novel HLA-B35 allele, which also has a point mutation in the translation initiation codon. J Immunol. 1992 Mar 15;148(6):1941–1948. [PubMed] [Google Scholar]
  43. Zemmour J., Parham P. Distinctive polymorphism at the HLA-C locus: implications for the expression of HLA-C. J Exp Med. 1992 Oct 1;176(4):937–950. doi: 10.1084/jem.176.4.937. [DOI] [PMC free article] [PubMed] [Google Scholar]

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