Interaction of α1 with α2 region in class I MHC proteins contributes determinants recognized by antibodies and cytotoxic T cells

I. Stroynowski, S. Clark, L. A. Henderson, L. Hood, M. McMillan, J. Forman

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

The structure-function relationship of individual coding regions of class I mouse major histocompatibility complex proteins was studied by a combination of recombinant DNA, gene transfer techniques, and serologic and functional characterization. To examine the role of α1 and α2 regions in antibody and CTL recognition, the third exon of H-2D(d), K(d), and L(d) transplantation antigen genes was replaced by the homologous coding region of the Qα-2-coded class I gene, Q6. We have chosen to carry out the exon shuffling experiments between these two different types of class I genes, because they are structurally similar and did not evolve to carry out identical functions. Therefore, it is less likely that the hybrid proteins well fortuitously recreate α1-α2 controlled functionally important determinants. The replacement of H-2 α2 coding region with its Q6 counterpart had different effects on the expression of the three genes. The mutant H-2D(d) gene transfected into L cells was expressed at high levels and retained several of the serologic determinants found on parental H-2D(d) and Q6 domains. The serologic epitopes on the mutant H-2K(d)-transfected cells were detectable at very low levels, whereas the product of the mutant H-2L(d) gene could not be identified at all. Analysis of cells transfected with mutant H-2D(d) gene with alloreactive and minor antigen(s)-restricted cytotoxic T cells indicated that the hybrid proteins lost the ability to be recognized by T cells. Our data suggest that cytotoxic T cells recognize conformational determinants composed of amino acids from α1 and α2 regions. Alternatively, it could be proposed that T cell recognition sites located in a single α1 or α2 protein region are susceptible to distortion upon α1-α2 interactions. Such susceptibility to conformational changes of the amino-terminal domain of transplantation antigens could be of functional importance for H-2-restricted antigen presentation.

Original languageEnglish (US)
Pages (from-to)2160-2166
Number of pages7
JournalJournal of Immunology
Volume135
Issue number3
StatePublished - 1985

Fingerprint

MHC Class I Genes
T-Lymphocytes
Histocompatibility Antigens
Antibodies
Genes
Exons
Proteins
H-2 Antigens
Gene Transfer Techniques
Recombinant DNA
Antigen Presentation
Major Histocompatibility Complex
Epitopes
Gene Expression
Antigens
Amino Acids

ASJC Scopus subject areas

  • Immunology

Cite this

Interaction of α1 with α2 region in class I MHC proteins contributes determinants recognized by antibodies and cytotoxic T cells. / Stroynowski, I.; Clark, S.; Henderson, L. A.; Hood, L.; McMillan, M.; Forman, J.

In: Journal of Immunology, Vol. 135, No. 3, 1985, p. 2160-2166.

Research output: Contribution to journalArticle

@article{b5412a59d8c54b1487c9c9b9cb0e5290,
title = "Interaction of α1 with α2 region in class I MHC proteins contributes determinants recognized by antibodies and cytotoxic T cells",
abstract = "The structure-function relationship of individual coding regions of class I mouse major histocompatibility complex proteins was studied by a combination of recombinant DNA, gene transfer techniques, and serologic and functional characterization. To examine the role of α1 and α2 regions in antibody and CTL recognition, the third exon of H-2D(d), K(d), and L(d) transplantation antigen genes was replaced by the homologous coding region of the Qα-2-coded class I gene, Q6. We have chosen to carry out the exon shuffling experiments between these two different types of class I genes, because they are structurally similar and did not evolve to carry out identical functions. Therefore, it is less likely that the hybrid proteins well fortuitously recreate α1-α2 controlled functionally important determinants. The replacement of H-2 α2 coding region with its Q6 counterpart had different effects on the expression of the three genes. The mutant H-2D(d) gene transfected into L cells was expressed at high levels and retained several of the serologic determinants found on parental H-2D(d) and Q6 domains. The serologic epitopes on the mutant H-2K(d)-transfected cells were detectable at very low levels, whereas the product of the mutant H-2L(d) gene could not be identified at all. Analysis of cells transfected with mutant H-2D(d) gene with alloreactive and minor antigen(s)-restricted cytotoxic T cells indicated that the hybrid proteins lost the ability to be recognized by T cells. Our data suggest that cytotoxic T cells recognize conformational determinants composed of amino acids from α1 and α2 regions. Alternatively, it could be proposed that T cell recognition sites located in a single α1 or α2 protein region are susceptible to distortion upon α1-α2 interactions. Such susceptibility to conformational changes of the amino-terminal domain of transplantation antigens could be of functional importance for H-2-restricted antigen presentation.",
author = "I. Stroynowski and S. Clark and Henderson, {L. A.} and L. Hood and M. McMillan and J. Forman",
year = "1985",
language = "English (US)",
volume = "135",
pages = "2160--2166",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "3",

}

TY - JOUR

T1 - Interaction of α1 with α2 region in class I MHC proteins contributes determinants recognized by antibodies and cytotoxic T cells

AU - Stroynowski, I.

AU - Clark, S.

AU - Henderson, L. A.

AU - Hood, L.

AU - McMillan, M.

AU - Forman, J.

PY - 1985

Y1 - 1985

N2 - The structure-function relationship of individual coding regions of class I mouse major histocompatibility complex proteins was studied by a combination of recombinant DNA, gene transfer techniques, and serologic and functional characterization. To examine the role of α1 and α2 regions in antibody and CTL recognition, the third exon of H-2D(d), K(d), and L(d) transplantation antigen genes was replaced by the homologous coding region of the Qα-2-coded class I gene, Q6. We have chosen to carry out the exon shuffling experiments between these two different types of class I genes, because they are structurally similar and did not evolve to carry out identical functions. Therefore, it is less likely that the hybrid proteins well fortuitously recreate α1-α2 controlled functionally important determinants. The replacement of H-2 α2 coding region with its Q6 counterpart had different effects on the expression of the three genes. The mutant H-2D(d) gene transfected into L cells was expressed at high levels and retained several of the serologic determinants found on parental H-2D(d) and Q6 domains. The serologic epitopes on the mutant H-2K(d)-transfected cells were detectable at very low levels, whereas the product of the mutant H-2L(d) gene could not be identified at all. Analysis of cells transfected with mutant H-2D(d) gene with alloreactive and minor antigen(s)-restricted cytotoxic T cells indicated that the hybrid proteins lost the ability to be recognized by T cells. Our data suggest that cytotoxic T cells recognize conformational determinants composed of amino acids from α1 and α2 regions. Alternatively, it could be proposed that T cell recognition sites located in a single α1 or α2 protein region are susceptible to distortion upon α1-α2 interactions. Such susceptibility to conformational changes of the amino-terminal domain of transplantation antigens could be of functional importance for H-2-restricted antigen presentation.

AB - The structure-function relationship of individual coding regions of class I mouse major histocompatibility complex proteins was studied by a combination of recombinant DNA, gene transfer techniques, and serologic and functional characterization. To examine the role of α1 and α2 regions in antibody and CTL recognition, the third exon of H-2D(d), K(d), and L(d) transplantation antigen genes was replaced by the homologous coding region of the Qα-2-coded class I gene, Q6. We have chosen to carry out the exon shuffling experiments between these two different types of class I genes, because they are structurally similar and did not evolve to carry out identical functions. Therefore, it is less likely that the hybrid proteins well fortuitously recreate α1-α2 controlled functionally important determinants. The replacement of H-2 α2 coding region with its Q6 counterpart had different effects on the expression of the three genes. The mutant H-2D(d) gene transfected into L cells was expressed at high levels and retained several of the serologic determinants found on parental H-2D(d) and Q6 domains. The serologic epitopes on the mutant H-2K(d)-transfected cells were detectable at very low levels, whereas the product of the mutant H-2L(d) gene could not be identified at all. Analysis of cells transfected with mutant H-2D(d) gene with alloreactive and minor antigen(s)-restricted cytotoxic T cells indicated that the hybrid proteins lost the ability to be recognized by T cells. Our data suggest that cytotoxic T cells recognize conformational determinants composed of amino acids from α1 and α2 regions. Alternatively, it could be proposed that T cell recognition sites located in a single α1 or α2 protein region are susceptible to distortion upon α1-α2 interactions. Such susceptibility to conformational changes of the amino-terminal domain of transplantation antigens could be of functional importance for H-2-restricted antigen presentation.

UR - http://www.scopus.com/inward/record.url?scp=0022345950&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0022345950&partnerID=8YFLogxK

M3 - Article

C2 - 2410513

AN - SCOPUS:0022345950

VL - 135

SP - 2160

EP - 2166

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 3

ER -