Amino Acid Substitutions Can Influence the Natural Killer (NK)-mediated Recognition of HLA-C Molecules. Role of Serine-77 and Lysine-80 in the Target Cell Protection from Lysis Mediated by "group 2" or "group 1" NK Clones

Overview

Journal J Exp Med

Specialties Allergy & Immunology
General Medicine

Date 1995 Aug 1

PMID 7629517

Citations 70

Authors

R Biassoni

M Falco

A CAMBIAGGI

P Costa

S Verdiani

D Pende

R Conte

C Di Donato

P Parham

L Moretta

Affiliations

Soon will be listed here.

Abstract

Natural killer (NK) cells have been shown to express a clonally distributed ability to recognize HLA class I alleles. The previously defined NK clones belonging to "group 1" recognize HLA-C*0401 (Cw4) and other HLA-C alleles sharing Asn at position 77 and Lys at position 80. Conversely, the "group 2" NK clones recognize HLA-Cw*0302 (Cw3) and other HLA-C alleles characterized by Ser at position 77 and Asn at position 80. We assessed directly the involvement of these two residues in the capacity of NK cell clones to discriminate between the two groups of HLA-C alleles. To this end, Cw3 and Cw4 alleles were subjected to site-directed mutagenesis. Substitution of the amino acids typical of the Cw3 allele (Ser-77 and Asn-80) with those present in Cw4 (Asn-77 and Lys-80) resulted in a Cw3 mutant that was no longer recognized by group 2 NK cell clones, but that was recognized by group 1 clones. Analysis of Cw3 or Cw4 molecules containing single amino acid substitutions indicates roles for Lys-80 in recognition mediated by group 1 clones and for Ser-77 in recognition mediated by group 2 clones. These results demonstrate that NK-mediated specific recognition of HLA-C allotypes is affected by single natural amino acid substitutions at positions 77 and 80 of the heavy chain.

Citing Articles

High KIR diversity in Uganda and Botswana children living with HIV.

Mukisa J, Kyobe S, Amujal M, Katagirya E, Diphoko T, Sebetso G bioRxiv. 2024; .

PMID: 39677597 PMC: 11642868. DOI: 10.1101/2024.12.03.626612.

Multifactorial determinants of NK cell repertoire organization: insights into age, sex, KIR genotype, HLA typing, and CMV influence.

Ferron E, David G, Willem C, Legrand N, Salameh P, Anquetil L Front Immunol. 2024; 15:1389358.

PMID: 38736873 PMC: 11082329. DOI: 10.3389/fimmu.2024.1389358.

Hepatocellular carcinoma after direct-acting antivirals for hepatitis C is associated with KIR-HLA types predicting weak NK cell-mediated immunity.

Ryan J, Haight C, Niemi E, Grab J, Dodge J, Lanier L Eur J Immunol. 2024; 54(8):e2350678.

PMID: 38700055 PMC: 11745084. DOI: 10.1002/eji.202350678.

Partitioning genetic effects on birthweight at classical human leukocyte antigen loci into maternal and fetal components, using structural equation modelling.

Wang G, Warrington N, Evans D Int J Epidemiol. 2023; 53(1).

PMID: 37831898 PMC: 10859143. DOI: 10.1093/ije/dyad142.

Role of the Killer Immunoglobulin-like Receptor and Human Leukocyte Antigen I Complex Polymorphisms in Kaposi Sarcoma-Associated Herpesvirus Infection.

Zhang X, Li Y, Han X, Xu Y, Wang H, Wang T Open Forum Infect Dis. 2023; 10(8):ofad435.

PMID: 37636520 PMC: 10456215. DOI: 10.1093/ofid/ofad435.

References

Trinchieri G . Biology of natural killer cells. Adv Immunol. 1989; 47:187-376. PMC: 7131425. DOI: 10.1016/s0065-2776(08)60664-1. View

Ho S, Hunt H, Horton R, Pullen J, Pease L . Site-directed mutagenesis by overlap extension using the polymerase chain reaction. Gene. 1989; 77(1):51-9. DOI: 10.1016/0378-1119(89)90358-2. View

Marsh S, Krausa P, Bodmer J . A preliminary analysis of the 11th International Histocompatibility Workshop monoclonal antibodies. Tissue Antigens. 1990; 36(4):180-6. DOI: 10.1111/j.1399-0039.1990.tb01827.x. View

Saper M, Bjorkman P, Wiley D . Refined structure of the human histocompatibility antigen HLA-A2 at 2.6 A resolution. J Mol Biol. 1991; 219(2):277-319. DOI: 10.1016/0022-2836(91)90567-p. View

Long E, Rosen-Bronson S, Karp D, Malnati M, Sekaly R, Jaraquemada D . Efficient cDNA expression vectors for stable and transient expression of HLA-DR in transfected fibroblast and lymphoid cells. Hum Immunol. 1991; 31(4):229-35. DOI: 10.1016/0198-8859(91)90092-n. View

Moretta L, Ciccone E, Moretta A, Hoglund P, Ohlen C, Karre K . Allorecognition by NK cells: nonself or no self?. Immunol Today. 1992; 13(8):300-6. DOI: 10.1016/0167-5699(92)90042-6. View

Colonna M, Spies T, Strominger J, Ciccone E, Moretta A, Moretta L . 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; 89(17):7983-5. PMC: 49839. DOI: 10.1073/pnas.89.17.7983. View

Zemmour J, Parham P . Distinctive polymorphism at the HLA-C locus: implications for the expression of HLA-C. J Exp Med. 1992; 176(4):937-50. PMC: 2119399. DOI: 10.1084/jem.176.4.937. View

Ciccone E, Pende D, Viale O, Than A, Di Donato C, Orengo A . Involvement of HLA class I alleles in natural killer (NK) cell-specific functions: expression of HLA-Cw3 confers selective protection from lysis by alloreactive NK clones displaying a defined specificity (specificity 2). J Exp Med. 1992; 176(4):963-71. PMC: 2119377. DOI: 10.1084/jem.176.4.963. View

10.

Zemmour J, Gumperz J, Hildebrand W, Ward F, Marsh S, Williams R . The molecular basis for reactivity of anti-Cw1 and anti-Cw3 alloantisera with HLA-B46 haplotypes. Tissue Antigens. 1992; 39(5):249-57. DOI: 10.1111/j.1399-0039.1992.tb01943.x. View

11.

Colonna M, Brooks E, Falco M, Ferrara G, Strominger J . Generation of allospecific natural killer cells by stimulation across a polymorphism of HLA-C. Science. 1993; 260(5111):1121-4. DOI: 10.1126/science.8493555. View

12.

Moretta A, Vitale M, Bottino C, Orengo A, Morelli L, Augugliaro R . P58 molecules as putative receptors for major histocompatibility complex (MHC) class I molecules in human natural killer (NK) cells. Anti-p58 antibodies reconstitute lysis of MHC class I-protected cells in NK clones displaying different specificities. J Exp Med. 1993; 178(2):597-604. PMC: 2191136. DOI: 10.1084/jem.178.2.597. View

13.

Christiansen F, Witt C, Ciccone E, Townend D, Pende D, Viale D . Human natural killer (NK) alloreactivity and its association with the major histocompatibility complex: ancestral haplotypes encode particular NK-defined haplotypes. J Exp Med. 1993; 178(3):1033-9. PMC: 2191171. DOI: 10.1084/jem.178.3.1033. View

14.

Moretta L, Ciccone E, Mingari M, Biassoni R, Moretta A . Human natural killer cells: origin, clonality, specificity, and receptors. Adv Immunol. 1994; 55:341-80. DOI: 10.1016/s0065-2776(08)60513-1. View

15.

Brodsky F, Parham P . Monomorphic anti-HLA-A,B,C monoclonal antibodies detecting molecular subunits and combinatorial determinants. J Immunol. 1982; 128(1):129-35. View

16.

Moretta A, Pantaleo G, Moretta L, Cerottini J, Mingari M . Direct demonstration of the clonogenic potential of every human peripheral blood T cell. Clonal analysis of HLA-DR expression and cytolytic activity. J Exp Med. 1983; 157(2):743-54. PMC: 2186923. DOI: 10.1084/jem.157.2.743. View

17.

Storkus W, Howell D, Salter R, Dawson J, Cresswell P . NK susceptibility varies inversely with target cell class I HLA antigen expression. J Immunol. 1987; 138(6):1657-9. View

18.

Bottino C, Tambussi G, Ferrini S, Ciccone E, Varese P, Mingari M . Two subsets of human T lymphocytes expressing gamma/delta antigen receptor are identifiable by monoclonal antibodies directed to two distinct molecular forms of the receptor. J Exp Med. 1988; 168(2):491-505. PMC: 2189015. DOI: 10.1084/jem.168.2.491. View

19.

Shimizu Y, Demars R . Production of human cells expressing individual transferred HLA-A,-B,-C genes using an HLA-A,-B,-C null human cell line. J Immunol. 1989; 142(9):3320-8. View

20.

Moretta A, Tambussi G, Bottino C, Tripodi G, Merli A, Ciccone E . A novel surface antigen expressed by a subset of human CD3- CD16+ natural killer cells. Role in cell activation and regulation of cytolytic function. J Exp Med. 1990; 171(3):695-714. PMC: 2187781. DOI: 10.1084/jem.171.3.695. View