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