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PMID: 8265660 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

HLA-C is the inhibitory ligand that determines dominant resistance to lysis by NK1- and NK2-specific natural killer cells.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 90 ·No. 24 ·1993-12-15 ·Pages 12000-4

Colonna M, Borsellino G, Falco M, Ferrara GB, Strominger JL

Abstract

Natural killer (NK) cells recognize alloantigens on normal cells. One of these alloantigens correlates with homozygosity for a dimorphism of HLA-C at positions 77-80, which is shared by a number of HLA-C alleles. A second allelic alloantigen correlates with homozygosity for the alternative HLA-C dimorphism, which is shared by the remaining HLA-C alleles. Moreover, NK1- and NK2-specific NK cell lines can be generated by mixed leukocyte cultures in which donor and stimulator are homozygous for the alternative dimorphisms at positions 77-80 of HLA-C. In the present work, the role of HLA-C in NK cell-mediated allorecognition was directly investigated by analyzing the effects produced by transfection of several HLA-C alleles on NK sensitivity of class I-deleted mutant cell lines. Transfection of cells with HLA-C alleles encoding Asn-77-Lys-80 (including HLA-Cw4, -Cw5, and -Cw6) inhibited the lysis of the targets by NK1-specific NK cells, whereas HLA-C alleles encoding Ser-77-Asn-80 (including HLA-Cw1, -Cw7, and -Cw13) protected the targets from NK2-specific NK cells. Thus, HLA-C alleles are the dominant inhibitory ligands that protect targets from lysis by these allospecific NK cells.

Related Genes
HLA-C HLA-Cw1 HLA-Cw13 HLA-Cw4 HLA-Cw5 HLA-Cw6 HLA-Cw7
MeSH Terms
Alleles Amino Acid Sequence Asparagine B-Lymphocytes Cell Line Cell Line, Transformed Cytotoxicity, Immunologic Gene Deletion Genes, MHC Class I HLA-C Antigens/genetics,metabolism Herpesvirus 4, Human/genetics Homozygote Humans Isoantigens/genetics Killer Cells, Natural/immunology Lymphocyte Culture Test, Mixed Major Histocompatibility Complex Point Mutation Serine Transfection
Chemicals
HLA-C Antigens Isoantigens Serine Asparagine
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Colonna M
Department of Biochemistry and Molecular Biology, Harvard University, Cambridge, MA 02138.
Borsellino G
Falco M
Ferrara G B
Strominger J L
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.90.24.12000
Published
1993-12-15
Pages
12000-4
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC48113
Subset
IM
Grants
NCI NIH HHS · CA 47554 · United States
NIDDK NIH HHS · DK 30241 · United States
External Links
PubMed source DOI: 10.1073/pnas.90.24.12000 PMC Full Text View journal details
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