TY - JOUR
T1 - Significance of the six peptide-binding pockets of HLA-A2.1 in influenza a matrix peptide-specific cytotoxic T-lymphocyte reactivity
AU - Matsui, Masanori
AU - Moots, Robert J.
AU - McMichael, Andrew J.
AU - Frelinger, Jeffrey A.
N1 - Funding Information:
ACKNOWLEDGMENTS We are grateful to Dr. P, Cresswell of Yale University for providing C1R cells, Dr. D. Klapper for preparation of FMP 58-66, Dr. D. Quinn and Dr. R. Warburton for critical reading of the manuscript, and Ms. K. LaPan and Ms. K. Pederson for excellent technical assistance. This work was supported by grants from the National Institute of Allergy and Infectious Diseases (AI-20288 and AI-29324), the Medical Research Council, and the North Atlantic Treaty Organization.
PY - 1994/10
Y1 - 1994/10
N2 - To evaluate the roles of the six peptide-binding pockets of HLA-A2.1 in FMP-specific CTL recognition, we have constructed an extensive library of HMy2.C1R cell lines expressing mutant HLA-A2.1 molecules with different amino acid substitutions in each of the six pockets. These cell lines were tested for their ability to present synthetic FMP 58-66 to FMP-specific, HLA-A2.1-restricted human CTL lines. Six of 12 mutants with amino acid changes in pocket B significantly affect the FMP-specific CTL recognition, suggesting that pocket B plays a critical role in FMP-specific CTL recognition. Surprisingly, mutations in all other pockets, except for pocket F, also have significant effects on the CTL recognition. These results suggest that even the shallow pockets, which are likely to be less critical for peptide binding than the deep pockets, play a crucial role in FMP-specific CTL recognition.
AB - To evaluate the roles of the six peptide-binding pockets of HLA-A2.1 in FMP-specific CTL recognition, we have constructed an extensive library of HMy2.C1R cell lines expressing mutant HLA-A2.1 molecules with different amino acid substitutions in each of the six pockets. These cell lines were tested for their ability to present synthetic FMP 58-66 to FMP-specific, HLA-A2.1-restricted human CTL lines. Six of 12 mutants with amino acid changes in pocket B significantly affect the FMP-specific CTL recognition, suggesting that pocket B plays a critical role in FMP-specific CTL recognition. Surprisingly, mutations in all other pockets, except for pocket F, also have significant effects on the CTL recognition. These results suggest that even the shallow pockets, which are likely to be less critical for peptide binding than the deep pockets, play a crucial role in FMP-specific CTL recognition.
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U2 - 10.1016/0198-8859(94)90010-8
DO - 10.1016/0198-8859(94)90010-8
M3 - Article
C2 - 7860362
AN - SCOPUS:0028019291
VL - 41
SP - 160
EP - 166
JO - Human Immunology
JF - Human Immunology
SN - 0198-8859
IS - 2
ER -