Single amino acid replacements in an antigenic peptide are sufficient to alter the TCR Vβ repertoire of the responding CD8+ cytotoxic lymphocyte population

Alexis M. Kalergis, Toshiro Ono, Fuming Wang, Teresa P. DiLorenzo, Shinichiro Honda, Stanley G. Nathenson

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Cytotoxic CD8+ T lymphocytes are activated upon the engagement of their Ag-specific receptors by MHC class I molecules loaded with peptides 8-11 amino acids long. T cell responses triggered by certain antigenic peptides are restricted to a limited number of TCR Vβ elements. The precise role of the peptide in causing this restricted TCR Vβ expansion in vivo remains unclear. To address this issue, we immunized C57BL/6 mice with the immunodominant peptide of the vesicular stomatitis virus (VSV) and several peptide variants carrying single substitutions at TCR-contact residues. We observed the expansion of a limited set of TCR Vβ elements responding to each peptide variant. To focus our analysis solely on the TCR β-chain, we created a transgenic mouse expressing exclusively the TCR α-chain from a VSV peptide-specific CD8+ T cell clone. These mice showed an even more restricted TCR Vβ usage consequent to peptide immunization. However, in both C57BL/6 and TCRα transgenic mice, single amino acid replacements in TCR- contact residues of the VSV peptide could alter the TCR Vβ usage of the responding CD8+ T lymphocytes. These results provide in vivo evidence for an interaction between the antigenic peptide and the germline-encoded complementarity-determining region-β loops that can influence the selection of the responding TCR repertoire. Furthermore, only replacements at residues near the C terminus of the peptide were able to alter the TCR Vβ usage, which is consistent with the notion that the TCR β-chain interacts in vivo preferentially with this region of the MHC/peptide complex.

Original languageEnglish (US)
Pages (from-to)7263-7270
Number of pages8
JournalJournal of Immunology
Volume162
Issue number12
StatePublished - Jun 15 1999

Fingerprint

Lymphocytes
Amino Acids
Peptides
Population
Vesicular Stomatitis
Viruses
T-Lymphocytes
Transgenic Mice
Complementarity Determining Regions
Cytotoxic T-Lymphocytes
Inbred C57BL Mouse
Immunization
Clone Cells

ASJC Scopus subject areas

  • Immunology

Cite this

Single amino acid replacements in an antigenic peptide are sufficient to alter the TCR Vβ repertoire of the responding CD8+ cytotoxic lymphocyte population. / Kalergis, Alexis M.; Ono, Toshiro; Wang, Fuming; DiLorenzo, Teresa P.; Honda, Shinichiro; Nathenson, Stanley G.

In: Journal of Immunology, Vol. 162, No. 12, 15.06.1999, p. 7263-7270.

Research output: Contribution to journalArticle

Kalergis, Alexis M. ; Ono, Toshiro ; Wang, Fuming ; DiLorenzo, Teresa P. ; Honda, Shinichiro ; Nathenson, Stanley G. / Single amino acid replacements in an antigenic peptide are sufficient to alter the TCR Vβ repertoire of the responding CD8+ cytotoxic lymphocyte population. In: Journal of Immunology. 1999 ; Vol. 162, No. 12. pp. 7263-7270.
@article{1fb6dd5280684c338a7c9f46f3c8864b,
title = "Single amino acid replacements in an antigenic peptide are sufficient to alter the TCR Vβ repertoire of the responding CD8+ cytotoxic lymphocyte population",
abstract = "Cytotoxic CD8+ T lymphocytes are activated upon the engagement of their Ag-specific receptors by MHC class I molecules loaded with peptides 8-11 amino acids long. T cell responses triggered by certain antigenic peptides are restricted to a limited number of TCR Vβ elements. The precise role of the peptide in causing this restricted TCR Vβ expansion in vivo remains unclear. To address this issue, we immunized C57BL/6 mice with the immunodominant peptide of the vesicular stomatitis virus (VSV) and several peptide variants carrying single substitutions at TCR-contact residues. We observed the expansion of a limited set of TCR Vβ elements responding to each peptide variant. To focus our analysis solely on the TCR β-chain, we created a transgenic mouse expressing exclusively the TCR α-chain from a VSV peptide-specific CD8+ T cell clone. These mice showed an even more restricted TCR Vβ usage consequent to peptide immunization. However, in both C57BL/6 and TCRα transgenic mice, single amino acid replacements in TCR- contact residues of the VSV peptide could alter the TCR Vβ usage of the responding CD8+ T lymphocytes. These results provide in vivo evidence for an interaction between the antigenic peptide and the germline-encoded complementarity-determining region-β loops that can influence the selection of the responding TCR repertoire. Furthermore, only replacements at residues near the C terminus of the peptide were able to alter the TCR Vβ usage, which is consistent with the notion that the TCR β-chain interacts in vivo preferentially with this region of the MHC/peptide complex.",
author = "Kalergis, {Alexis M.} and Toshiro Ono and Fuming Wang and DiLorenzo, {Teresa P.} and Shinichiro Honda and Nathenson, {Stanley G.}",
year = "1999",
month = "6",
day = "15",
language = "English (US)",
volume = "162",
pages = "7263--7270",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "12",

}

TY - JOUR

T1 - Single amino acid replacements in an antigenic peptide are sufficient to alter the TCR Vβ repertoire of the responding CD8+ cytotoxic lymphocyte population

AU - Kalergis, Alexis M.

AU - Ono, Toshiro

AU - Wang, Fuming

AU - DiLorenzo, Teresa P.

AU - Honda, Shinichiro

AU - Nathenson, Stanley G.

PY - 1999/6/15

Y1 - 1999/6/15

N2 - Cytotoxic CD8+ T lymphocytes are activated upon the engagement of their Ag-specific receptors by MHC class I molecules loaded with peptides 8-11 amino acids long. T cell responses triggered by certain antigenic peptides are restricted to a limited number of TCR Vβ elements. The precise role of the peptide in causing this restricted TCR Vβ expansion in vivo remains unclear. To address this issue, we immunized C57BL/6 mice with the immunodominant peptide of the vesicular stomatitis virus (VSV) and several peptide variants carrying single substitutions at TCR-contact residues. We observed the expansion of a limited set of TCR Vβ elements responding to each peptide variant. To focus our analysis solely on the TCR β-chain, we created a transgenic mouse expressing exclusively the TCR α-chain from a VSV peptide-specific CD8+ T cell clone. These mice showed an even more restricted TCR Vβ usage consequent to peptide immunization. However, in both C57BL/6 and TCRα transgenic mice, single amino acid replacements in TCR- contact residues of the VSV peptide could alter the TCR Vβ usage of the responding CD8+ T lymphocytes. These results provide in vivo evidence for an interaction between the antigenic peptide and the germline-encoded complementarity-determining region-β loops that can influence the selection of the responding TCR repertoire. Furthermore, only replacements at residues near the C terminus of the peptide were able to alter the TCR Vβ usage, which is consistent with the notion that the TCR β-chain interacts in vivo preferentially with this region of the MHC/peptide complex.

AB - Cytotoxic CD8+ T lymphocytes are activated upon the engagement of their Ag-specific receptors by MHC class I molecules loaded with peptides 8-11 amino acids long. T cell responses triggered by certain antigenic peptides are restricted to a limited number of TCR Vβ elements. The precise role of the peptide in causing this restricted TCR Vβ expansion in vivo remains unclear. To address this issue, we immunized C57BL/6 mice with the immunodominant peptide of the vesicular stomatitis virus (VSV) and several peptide variants carrying single substitutions at TCR-contact residues. We observed the expansion of a limited set of TCR Vβ elements responding to each peptide variant. To focus our analysis solely on the TCR β-chain, we created a transgenic mouse expressing exclusively the TCR α-chain from a VSV peptide-specific CD8+ T cell clone. These mice showed an even more restricted TCR Vβ usage consequent to peptide immunization. However, in both C57BL/6 and TCRα transgenic mice, single amino acid replacements in TCR- contact residues of the VSV peptide could alter the TCR Vβ usage of the responding CD8+ T lymphocytes. These results provide in vivo evidence for an interaction between the antigenic peptide and the germline-encoded complementarity-determining region-β loops that can influence the selection of the responding TCR repertoire. Furthermore, only replacements at residues near the C terminus of the peptide were able to alter the TCR Vβ usage, which is consistent with the notion that the TCR β-chain interacts in vivo preferentially with this region of the MHC/peptide complex.

UR - http://www.scopus.com/inward/record.url?scp=0033564254&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033564254&partnerID=8YFLogxK

M3 - Article

C2 - 10358174

AN - SCOPUS:0033564254

VL - 162

SP - 7263

EP - 7270

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 12

ER -