Inhibition of allorecognition by an H-2Kb-derived peptide is evidence for a T-cell binding region on a major histocompatibility complex molecule

Jonathan P Schneck, T. Munitz, J. E. Coligan, W. L. Maloy, D. H. Margulies, A. Singer

Research output: Contribution to journalArticle

Abstract

The class I and class II major histocompatibility complex (MHC) antigens are polymorphic cell-surface glycoproteins that present antigenic peptides to T lymphocytes in the generation of immune responses. While much is known about the recognition and processing of antigens, the nature of T-cell recognition sites on MHC molecules is poorly understood. Both structural and functional studies have suggested that the two major α-helical regions of the class I MHC molecule not only define the site for binding of antigenic peptide but also provide potential sites for interaction of the MHC molecule with the T-cell receptor. A peptide derived from one of these regions on the H-2Kb molecule, peptide Kb163-174, was previously shown to specifically inhibit the stimulation of an alloreactive T-cell hybridoma. To further investigate the role of this region in the recognition of H-2Kb, the effects of peptide Kb163-174 on allospecific T-cell lines and clones were studied. When peptide Kb163-174 was cocultured with either an H-2K(bm10) anti-H-2Kb cytotoxic T-lymphocyte (CTL) clone or a CTL line, this peptide inhibited lysis of H-2Kb targets. Pretreatment experiments showed that the blockade was due to interaction of the peptide with the effector T cells. Surprisingly, peptide Kb163-174 also inhibited lysis of H-2Kb targets by H2-K(bm1)-, H-2K(bm3), H-2K(bm6)-, and H-2K(bm8)-anti-H-2Kb CTLs. These CTLs, which identify multiple antigenic sites on H-2Kb in the α1 and α2 domains, are not directed against amino acid residues 163-174 of H-2Kb. In addition, peptide Kb163-174 specifically blocked lysis of only H-2Kb and not H-2L(d) targets by a single bulk CTL culture that was alloreactive on both H-2Kb and H-2L(d). These results indicate that peptide Kb(163-174) interferes with T-cell receptor engagement of a contact site on the H-2Kb molecule. Thus, amino acid residues 163-174 define a site used by many alloreactive T cells to engage the H-2Kb molecule.

Original languageEnglish (US)
Pages (from-to)8516-8520
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume86
Issue number21
StatePublished - 1989
Externally publishedYes

Fingerprint

Major Histocompatibility Complex
T-Lymphocytes
Peptides
Cytotoxic T-Lymphocytes
T-Cell Antigen Receptor
Clone Cells
Peptide T
Amino Acids
Histocompatibility Antigens Class II
Membrane Glycoproteins
Antigen Presentation
Hybridomas
Binding Sites
Cell Line

ASJC Scopus subject areas

  • General
  • Genetics

Cite this

Inhibition of allorecognition by an H-2Kb-derived peptide is evidence for a T-cell binding region on a major histocompatibility complex molecule. / Schneck, Jonathan P; Munitz, T.; Coligan, J. E.; Maloy, W. L.; Margulies, D. H.; Singer, A.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 86, No. 21, 1989, p. 8516-8520.

Research output: Contribution to journalArticle

@article{b6e227283adf462a994dc1b02705437f,
title = "Inhibition of allorecognition by an H-2Kb-derived peptide is evidence for a T-cell binding region on a major histocompatibility complex molecule",
abstract = "The class I and class II major histocompatibility complex (MHC) antigens are polymorphic cell-surface glycoproteins that present antigenic peptides to T lymphocytes in the generation of immune responses. While much is known about the recognition and processing of antigens, the nature of T-cell recognition sites on MHC molecules is poorly understood. Both structural and functional studies have suggested that the two major α-helical regions of the class I MHC molecule not only define the site for binding of antigenic peptide but also provide potential sites for interaction of the MHC molecule with the T-cell receptor. A peptide derived from one of these regions on the H-2Kb molecule, peptide Kb163-174, was previously shown to specifically inhibit the stimulation of an alloreactive T-cell hybridoma. To further investigate the role of this region in the recognition of H-2Kb, the effects of peptide Kb163-174 on allospecific T-cell lines and clones were studied. When peptide Kb163-174 was cocultured with either an H-2K(bm10) anti-H-2Kb cytotoxic T-lymphocyte (CTL) clone or a CTL line, this peptide inhibited lysis of H-2Kb targets. Pretreatment experiments showed that the blockade was due to interaction of the peptide with the effector T cells. Surprisingly, peptide Kb163-174 also inhibited lysis of H-2Kb targets by H2-K(bm1)-, H-2K(bm3), H-2K(bm6)-, and H-2K(bm8)-anti-H-2Kb CTLs. These CTLs, which identify multiple antigenic sites on H-2Kb in the α1 and α2 domains, are not directed against amino acid residues 163-174 of H-2Kb. In addition, peptide Kb163-174 specifically blocked lysis of only H-2Kb and not H-2L(d) targets by a single bulk CTL culture that was alloreactive on both H-2Kb and H-2L(d). These results indicate that peptide Kb(163-174) interferes with T-cell receptor engagement of a contact site on the H-2Kb molecule. Thus, amino acid residues 163-174 define a site used by many alloreactive T cells to engage the H-2Kb molecule.",
author = "Schneck, {Jonathan P} and T. Munitz and Coligan, {J. E.} and Maloy, {W. L.} and Margulies, {D. H.} and A. Singer",
year = "1989",
language = "English (US)",
volume = "86",
pages = "8516--8520",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "21",

}

TY - JOUR

T1 - Inhibition of allorecognition by an H-2Kb-derived peptide is evidence for a T-cell binding region on a major histocompatibility complex molecule

AU - Schneck, Jonathan P

AU - Munitz, T.

AU - Coligan, J. E.

AU - Maloy, W. L.

AU - Margulies, D. H.

AU - Singer, A.

PY - 1989

Y1 - 1989

N2 - The class I and class II major histocompatibility complex (MHC) antigens are polymorphic cell-surface glycoproteins that present antigenic peptides to T lymphocytes in the generation of immune responses. While much is known about the recognition and processing of antigens, the nature of T-cell recognition sites on MHC molecules is poorly understood. Both structural and functional studies have suggested that the two major α-helical regions of the class I MHC molecule not only define the site for binding of antigenic peptide but also provide potential sites for interaction of the MHC molecule with the T-cell receptor. A peptide derived from one of these regions on the H-2Kb molecule, peptide Kb163-174, was previously shown to specifically inhibit the stimulation of an alloreactive T-cell hybridoma. To further investigate the role of this region in the recognition of H-2Kb, the effects of peptide Kb163-174 on allospecific T-cell lines and clones were studied. When peptide Kb163-174 was cocultured with either an H-2K(bm10) anti-H-2Kb cytotoxic T-lymphocyte (CTL) clone or a CTL line, this peptide inhibited lysis of H-2Kb targets. Pretreatment experiments showed that the blockade was due to interaction of the peptide with the effector T cells. Surprisingly, peptide Kb163-174 also inhibited lysis of H-2Kb targets by H2-K(bm1)-, H-2K(bm3), H-2K(bm6)-, and H-2K(bm8)-anti-H-2Kb CTLs. These CTLs, which identify multiple antigenic sites on H-2Kb in the α1 and α2 domains, are not directed against amino acid residues 163-174 of H-2Kb. In addition, peptide Kb163-174 specifically blocked lysis of only H-2Kb and not H-2L(d) targets by a single bulk CTL culture that was alloreactive on both H-2Kb and H-2L(d). These results indicate that peptide Kb(163-174) interferes with T-cell receptor engagement of a contact site on the H-2Kb molecule. Thus, amino acid residues 163-174 define a site used by many alloreactive T cells to engage the H-2Kb molecule.

AB - The class I and class II major histocompatibility complex (MHC) antigens are polymorphic cell-surface glycoproteins that present antigenic peptides to T lymphocytes in the generation of immune responses. While much is known about the recognition and processing of antigens, the nature of T-cell recognition sites on MHC molecules is poorly understood. Both structural and functional studies have suggested that the two major α-helical regions of the class I MHC molecule not only define the site for binding of antigenic peptide but also provide potential sites for interaction of the MHC molecule with the T-cell receptor. A peptide derived from one of these regions on the H-2Kb molecule, peptide Kb163-174, was previously shown to specifically inhibit the stimulation of an alloreactive T-cell hybridoma. To further investigate the role of this region in the recognition of H-2Kb, the effects of peptide Kb163-174 on allospecific T-cell lines and clones were studied. When peptide Kb163-174 was cocultured with either an H-2K(bm10) anti-H-2Kb cytotoxic T-lymphocyte (CTL) clone or a CTL line, this peptide inhibited lysis of H-2Kb targets. Pretreatment experiments showed that the blockade was due to interaction of the peptide with the effector T cells. Surprisingly, peptide Kb163-174 also inhibited lysis of H-2Kb targets by H2-K(bm1)-, H-2K(bm3), H-2K(bm6)-, and H-2K(bm8)-anti-H-2Kb CTLs. These CTLs, which identify multiple antigenic sites on H-2Kb in the α1 and α2 domains, are not directed against amino acid residues 163-174 of H-2Kb. In addition, peptide Kb163-174 specifically blocked lysis of only H-2Kb and not H-2L(d) targets by a single bulk CTL culture that was alloreactive on both H-2Kb and H-2L(d). These results indicate that peptide Kb(163-174) interferes with T-cell receptor engagement of a contact site on the H-2Kb molecule. Thus, amino acid residues 163-174 define a site used by many alloreactive T cells to engage the H-2Kb molecule.

UR - http://www.scopus.com/inward/record.url?scp=0039375065&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0039375065&partnerID=8YFLogxK

M3 - Article

C2 - 2813409

AN - SCOPUS:0039375065

VL - 86

SP - 8516

EP - 8520

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 21

ER -