FUNCTIONAL-SIGNIFICANCE OF VARIED QUANTITATIVE AND QUALITATIVE EXPRESSION OF HLA-A2.1 ANTIGENS IN DETERMINING THE SUSCEPTIBILITY OF CELLS TO CYTOTOXIC T-LYMPHOCYTES

Citation
Dc. Shieh et al., FUNCTIONAL-SIGNIFICANCE OF VARIED QUANTITATIVE AND QUALITATIVE EXPRESSION OF HLA-A2.1 ANTIGENS IN DETERMINING THE SUSCEPTIBILITY OF CELLS TO CYTOTOXIC T-LYMPHOCYTES, Human immunology, 46(1), 1996, pp. 18-26
Citations number
28
Categorie Soggetti
Immunology
Journal title
ISSN journal
01988859
Volume
46
Issue
1
Year of publication
1996
Pages
18 - 26
Database
ISI
SICI code
0198-8859(1996)46:1<18:FOVQAQ>2.0.ZU;2-5
Abstract
To determine whether varied quantitative HLA expression affects the su sceptibility of target cells to CTLs, a panel of 15 EBV-transformed ly mphoblastoid cell lines expressing a fivefold difference of surface HL A-A2.1 antigens were employed. The susceptibility of these cell lines to HLA-A2.1-resrricted and influenza virus matrix peptide-specific CTL s was correlated with the amounts of HLA-A2.1 antigens expressed on th eir surface. The results show a linear correlation between both parame ters using exogenous viral peptide. The same linear correlation was ob served when target cells infected with influenza virus were studied. T hese findings support che hypothesis that the amount of HLA antigens e xpressed on the cell surface is functionally significant in determinin g the susceptibility of target cells to CTLs. During our study, we als o found that two HLA-A-2.1-positive cell lines were unresponsive to th e CTL. Further investigation of the amino acid sequences of these cell lines reveals that their HLA-A2.1. antigens belong to the HLA-A0207 s ubtype which is different from HLA-A0201(A2.1) by one nucleotide. This difference results in an amino acid substitution from tyrosine to cys teine at position 99 of HLA-A2.1 heavy chains. Using a peptide-induced reconstitution assay, it was shown that failure of the peptide bindin g is responsible for the absence of cytotoxicity. This finding support s the hypothesis that amino acid 99 plays an important role in determi ning the peptide-binding specificity of HLA-A2 molecules.