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The alpha 1/alpha 2 domains of class I HLA molecules confer resistance to natural killing.

W J Storkus, J Alexander, J A Payne, P Cresswell and J R Dawson
J Immunol December 1, 1989, 143 (11) 3853-3857;
W J Storkus
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J Alexander
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J A Payne
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P Cresswell
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J R Dawson
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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-2Dp 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 alpha 1 and alpha 2 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.

  • Copyright © 1989 by American Association of Immunologists

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The Journal of Immunology
Vol. 143, Issue 11
1 Dec 1989
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The alpha 1/alpha 2 domains of class I HLA molecules confer resistance to natural killing.
W J Storkus, J Alexander, J A Payne, P Cresswell, J R Dawson
The Journal of Immunology December 1, 1989, 143 (11) 3853-3857;

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The alpha 1/alpha 2 domains of class I HLA molecules confer resistance to natural killing.
W J Storkus, J Alexander, J A Payne, P Cresswell, J R Dawson
The Journal of Immunology December 1, 1989, 143 (11) 3853-3857;
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