The α1/α2 domains of class I HLA molecules confer resistance to natural killing

W. J. Storkus, J. Alexander, John A Payne, P. Cresswell, J. R. Dawson

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94 Scopus citations

Abstract

The expression of transfected HLA class I Ag has previously been shown to protect human target cells from NK-mediated conjugation and cytolysis. In this same system, transfected H-2 class I Ag fail to impart resistance to NK. In this study, we have mapped the portion of the HLA class I molecule involved in this protective effect by exploiting this HLA/H-2 dichotomy. Hybrid class I genes were produced by exon-shuffling between the HLA-B7 and H-2D(p) genes, and transfected into the class I Ag-deficient B-lymphoblastoid cell line (B-LCL) C1R. Only those transfectants expressing class I Ag containing the α1 and α2 domains of the HLA molecule are protected from NK, suggesting the 'protective epitope' is located within these domains. Since a glycosylation difference exists between HLA and H-2 class I Ag within these domains (i.e., at amino acid residue 176), the role of carbohydrate in the class I protective effect was examined. HLA-B7 mutant genes encoding proteins which either lack the normal carbohydrate addition site at amino acid residue 86 (B7M86-) or possess an additional site at residue 176 (B7M176+) were transfected into C1R. Transfectants expressing either mutant HLA-B7 Ag were protected from NK. Thus, carbohydrate is probably not integral to a class I 'protective epitope'. The potential for allelic variation in the ability of HLA class I Ag to protect C1R target cells from NK was examined in HLA-A2, A3, B7, and Bw58 transfectants. Although no significant variation exists among the HLA-A3, B7, and Bw58 alleles, HLA-A2 appears unable to protect. Comparison of amino acid sequences suggests a restricted number of residues which may be relevant to the protective effect.

Original languageEnglish (US)
Pages (from-to)3853-3857
Number of pages5
JournalJournal of Immunology
Volume143
Issue number11
StatePublished - 1989
Externally publishedYes

ASJC Scopus subject areas

  • Immunology

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    Storkus, W. J., Alexander, J., Payne, J. A., Cresswell, P., & Dawson, J. R. (1989). The α1/α2 domains of class I HLA molecules confer resistance to natural killing. Journal of Immunology, 143(11), 3853-3857.