A cluster of mutations in HLA-A2 α2 helix abolishes peptide recognition by T cells

Robert J. Moots, Masanori Matsui, Laszlo Pazmany, Andrew J. McMichael, Jeffrey A Frelinger

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

In order to investigate the regions of HLA-A2 that control peptide-specific cytotoxic T lymphocyte (CTL) recognition, 37 HLA-A2 genes coding for 50 point mutations that span the α2 helix were synthesized by the technique of saturation mutagenesis. Twenty-nine of these genes, which code for 41 point mutations, were transfected into C1R cells and used as targets in cytotoxicity assays, in the presence of influenza-A matrix peptide 58-68 with specific CTL as effectors. All the transfectants were recognized fully by matrix peptide-specific CTL apart from those with amino acid substitutions at positions 152, 154, 155, 156, or 161, which led to a total loss of recognition and those with mutations at residue 27 or a double mutation at 138 and 150, which were recognized in an intermediate manner. The clustering of the crucial residues that emerges may reflect direct interaction of their side-chains with peptide or the CTL receptor.

Original languageEnglish (US)
Pages (from-to)141-148
Number of pages8
JournalImmunogenetics
Volume34
Issue number3
DOIs
StatePublished - Sep 1991
Externally publishedYes

Fingerprint

Peptide T
HLA-A2 Antigen
Cytotoxic T-Lymphocytes
T-Lymphocytes
Peptides
Mutation
Point Mutation
Amino Acid Substitution
Mutagenesis
Human Influenza
Genes
Cluster Analysis

ASJC Scopus subject areas

  • Immunology
  • Genetics

Cite this

A cluster of mutations in HLA-A2 α2 helix abolishes peptide recognition by T cells. / Moots, Robert J.; Matsui, Masanori; Pazmany, Laszlo; McMichael, Andrew J.; Frelinger, Jeffrey A.

In: Immunogenetics, Vol. 34, No. 3, 09.1991, p. 141-148.

Research output: Contribution to journalArticle

Moots, Robert J. ; Matsui, Masanori ; Pazmany, Laszlo ; McMichael, Andrew J. ; Frelinger, Jeffrey A. / A cluster of mutations in HLA-A2 α2 helix abolishes peptide recognition by T cells. In: Immunogenetics. 1991 ; Vol. 34, No. 3. pp. 141-148.
@article{2f4d1db0f30c45c98c03e0586048ffe7,
title = "A cluster of mutations in HLA-A2 α2 helix abolishes peptide recognition by T cells",
abstract = "In order to investigate the regions of HLA-A2 that control peptide-specific cytotoxic T lymphocyte (CTL) recognition, 37 HLA-A2 genes coding for 50 point mutations that span the α2 helix were synthesized by the technique of saturation mutagenesis. Twenty-nine of these genes, which code for 41 point mutations, were transfected into C1R cells and used as targets in cytotoxicity assays, in the presence of influenza-A matrix peptide 58-68 with specific CTL as effectors. All the transfectants were recognized fully by matrix peptide-specific CTL apart from those with amino acid substitutions at positions 152, 154, 155, 156, or 161, which led to a total loss of recognition and those with mutations at residue 27 or a double mutation at 138 and 150, which were recognized in an intermediate manner. The clustering of the crucial residues that emerges may reflect direct interaction of their side-chains with peptide or the CTL receptor.",
author = "Moots, {Robert J.} and Masanori Matsui and Laszlo Pazmany and McMichael, {Andrew J.} and Frelinger, {Jeffrey A}",
year = "1991",
month = "9",
doi = "10.1007/BF00205816",
language = "English (US)",
volume = "34",
pages = "141--148",
journal = "Immunogenetics",
issn = "0093-7711",
publisher = "Springer Verlag",
number = "3",

}

TY - JOUR

T1 - A cluster of mutations in HLA-A2 α2 helix abolishes peptide recognition by T cells

AU - Moots, Robert J.

AU - Matsui, Masanori

AU - Pazmany, Laszlo

AU - McMichael, Andrew J.

AU - Frelinger, Jeffrey A

PY - 1991/9

Y1 - 1991/9

N2 - In order to investigate the regions of HLA-A2 that control peptide-specific cytotoxic T lymphocyte (CTL) recognition, 37 HLA-A2 genes coding for 50 point mutations that span the α2 helix were synthesized by the technique of saturation mutagenesis. Twenty-nine of these genes, which code for 41 point mutations, were transfected into C1R cells and used as targets in cytotoxicity assays, in the presence of influenza-A matrix peptide 58-68 with specific CTL as effectors. All the transfectants were recognized fully by matrix peptide-specific CTL apart from those with amino acid substitutions at positions 152, 154, 155, 156, or 161, which led to a total loss of recognition and those with mutations at residue 27 or a double mutation at 138 and 150, which were recognized in an intermediate manner. The clustering of the crucial residues that emerges may reflect direct interaction of their side-chains with peptide or the CTL receptor.

AB - In order to investigate the regions of HLA-A2 that control peptide-specific cytotoxic T lymphocyte (CTL) recognition, 37 HLA-A2 genes coding for 50 point mutations that span the α2 helix were synthesized by the technique of saturation mutagenesis. Twenty-nine of these genes, which code for 41 point mutations, were transfected into C1R cells and used as targets in cytotoxicity assays, in the presence of influenza-A matrix peptide 58-68 with specific CTL as effectors. All the transfectants were recognized fully by matrix peptide-specific CTL apart from those with amino acid substitutions at positions 152, 154, 155, 156, or 161, which led to a total loss of recognition and those with mutations at residue 27 or a double mutation at 138 and 150, which were recognized in an intermediate manner. The clustering of the crucial residues that emerges may reflect direct interaction of their side-chains with peptide or the CTL receptor.

UR - http://www.scopus.com/inward/record.url?scp=0025824375&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0025824375&partnerID=8YFLogxK

U2 - 10.1007/BF00205816

DO - 10.1007/BF00205816

M3 - Article

C2 - 1894308

AN - SCOPUS:0025824375

VL - 34

SP - 141

EP - 148

JO - Immunogenetics

JF - Immunogenetics

SN - 0093-7711

IS - 3

ER -