Roles of the six peptide-binding pockets of the HLA-A2 molecule in allorecognition by human cytotoxic T-cell clones

Masanori Matsui, Catarina E. Hioe, Jeffrey A Frelinger

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52 Citations (Scopus)

Abstract

To evaluate the contribution of the major histocompatibility complex class I pockets to the binding of self-peptides recognized by alloreactive cytotoxic T-lymphocyte (CTL) clones, we have constructed an extensive library of HLA-A2 mutants with different amino acid substitutions in each of the six pockets. When these mutants were tested in cytotoxicity assays with a panel of HLA-A2 -specific alloreactive CTL clones, each CTL clone showed a unique pattern of reactivity, implying the different contributions of each pocket to binding individual peptides. We noted that the majority of the mutants in pocket B significantly affect recognition by the CTL clones. Unexpectedly, the mutations influencing allorecognition are found in all other pockets as well. Overall, this study demonstrates that each of the six peptide-binding pockets plays an important and distinct role in binding of self-peptides required for recognition of the HLA-A2 molecule by alloreactive CTLs.

Original languageEnglish (US)
Pages (from-to)674-678
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume90
Issue number2
StatePublished - Jan 15 1993
Externally publishedYes

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HLA-A2 Antigen
Cytotoxic T-Lymphocytes
Clone Cells
T-Lymphocytes
Peptides
Amino Acid Substitution
Major Histocompatibility Complex
Mutation

ASJC Scopus subject areas

  • General
  • Genetics

Cite this

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abstract = "To evaluate the contribution of the major histocompatibility complex class I pockets to the binding of self-peptides recognized by alloreactive cytotoxic T-lymphocyte (CTL) clones, we have constructed an extensive library of HLA-A2 mutants with different amino acid substitutions in each of the six pockets. When these mutants were tested in cytotoxicity assays with a panel of HLA-A2 -specific alloreactive CTL clones, each CTL clone showed a unique pattern of reactivity, implying the different contributions of each pocket to binding individual peptides. We noted that the majority of the mutants in pocket B significantly affect recognition by the CTL clones. Unexpectedly, the mutations influencing allorecognition are found in all other pockets as well. Overall, this study demonstrates that each of the six peptide-binding pockets plays an important and distinct role in binding of self-peptides required for recognition of the HLA-A2 molecule by alloreactive CTLs.",
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AU - Frelinger, Jeffrey A

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