Human T-cell receptor (TCR) α/β+ CD4-CD8- T cells express oligoclonal TCRs, share junctional motifs across TCR Vβ-gene families, and phenotypically resemble memory T cells

Edward G Brooks, Steven P. Balk, Karine Aupeix, Marco Colonna, Jack L. Strominger, Veronika Groh-Spies

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

Original languageEnglish
Pages (from-to)11787-11791
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume90
Issue number24
StatePublished - Dec 15 1993
Externally publishedYes

Fingerprint

T-Cell Receptor Genes
T-Cell Antigen Receptor
T-Lymphocytes
CD45 Antigens
Genes
Amino Acid Motifs
HLA-DR Antigens
Autoimmune Diseases

ASJC Scopus subject areas

  • General
  • Genetics

Cite this

Human T-cell receptor (TCR) α/β+ CD4-CD8- T cells express oligoclonal TCRs, share junctional motifs across TCR Vβ-gene families, and phenotypically resemble memory T cells. / Brooks, Edward G; Balk, Steven P.; Aupeix, Karine; Colonna, Marco; Strominger, Jack L.; Groh-Spies, Veronika.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 90, No. 24, 15.12.1993, p. 11787-11791.

Research output: Contribution to journalArticle

@article{673e0f51a87449f485c1203f2dfb2a23,
title = "Human T-cell receptor (TCR) α/β+ CD4-CD8- T cells express oligoclonal TCRs, share junctional motifs across TCR Vβ-gene families, and phenotypically resemble memory T cells",
abstract = "Most human T cells express the TCR α/β and either CD4 or CD8 molecules (single positive, SP); however, small numbers lack CD4 and CD8. In inbred mice, α/β CD4-CD8- (double negative, DN) T cells preferentially express certain β variable region (Vβ) families and may arise via unique developmental pathways. Increased percentages of α/β DN T cells have been identified in some human and murine autoimmune and immunodeficiency diseases. However, their contribution to disease pathology or normal immunity is unknown. To study the cell surface phenotype and TCR diversity of human α/β DN T cells, these cells were isolated from the peripheral blood of healthy adults. The proportion of α/β DN T cells expressing molecules associated with activation (HLA-DR), previous exposure to antigen (CD45RO), and cytotoxic function (CD56, CD57, and CD11b) was increased relative to SP T cells. The TCR Vβ repertoire of α/β DN T cells was different from that of α/β SP T cells, although most major gene families were present. For example, higher proportions of Vβ11, a minor gene family in peripheral blood leukocytes, were found in most α/β DN T-cell samples. In contrast to mice, no dominant Vβ family was used consistently in different human individuals. Within an individual α/β DN T cells possessed an oligoclonal TCRβ repertoire with conservation of several distinct junctional amino acid motifs with one joined to three different Vβ genes in two individuals, suggesting that these cells have undergone a selection process driven by a limited set of ligands. The possibility that they may represent, at least in part, originally SP T cells anergized by down-modulation of CD4 or CD8 must also be entertained. Overall, this study demonstrates that human peripheral blood α/β DN T cells possess unique phenotypic and TCRβ repertoire characteristics when compared with the major α/β SP T cell populations and thus may serve specialized immunologic functions and/or have an unusual origin.",
author = "Brooks, {Edward G} and Balk, {Steven P.} and Karine Aupeix and Marco Colonna and Strominger, {Jack L.} and Veronika Groh-Spies",
year = "1993",
month = "12",
day = "15",
language = "English",
volume = "90",
pages = "11787--11791",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "24",

}

TY - JOUR

T1 - Human T-cell receptor (TCR) α/β+ CD4-CD8- T cells express oligoclonal TCRs, share junctional motifs across TCR Vβ-gene families, and phenotypically resemble memory T cells

AU - Brooks, Edward G

AU - Balk, Steven P.

AU - Aupeix, Karine

AU - Colonna, Marco

AU - Strominger, Jack L.

AU - Groh-Spies, Veronika

PY - 1993/12/15

Y1 - 1993/12/15

N2 - Most human T cells express the TCR α/β and either CD4 or CD8 molecules (single positive, SP); however, small numbers lack CD4 and CD8. In inbred mice, α/β CD4-CD8- (double negative, DN) T cells preferentially express certain β variable region (Vβ) families and may arise via unique developmental pathways. Increased percentages of α/β DN T cells have been identified in some human and murine autoimmune and immunodeficiency diseases. However, their contribution to disease pathology or normal immunity is unknown. To study the cell surface phenotype and TCR diversity of human α/β DN T cells, these cells were isolated from the peripheral blood of healthy adults. The proportion of α/β DN T cells expressing molecules associated with activation (HLA-DR), previous exposure to antigen (CD45RO), and cytotoxic function (CD56, CD57, and CD11b) was increased relative to SP T cells. The TCR Vβ repertoire of α/β DN T cells was different from that of α/β SP T cells, although most major gene families were present. For example, higher proportions of Vβ11, a minor gene family in peripheral blood leukocytes, were found in most α/β DN T-cell samples. In contrast to mice, no dominant Vβ family was used consistently in different human individuals. Within an individual α/β DN T cells possessed an oligoclonal TCRβ repertoire with conservation of several distinct junctional amino acid motifs with one joined to three different Vβ genes in two individuals, suggesting that these cells have undergone a selection process driven by a limited set of ligands. The possibility that they may represent, at least in part, originally SP T cells anergized by down-modulation of CD4 or CD8 must also be entertained. Overall, this study demonstrates that human peripheral blood α/β DN T cells possess unique phenotypic and TCRβ repertoire characteristics when compared with the major α/β SP T cell populations and thus may serve specialized immunologic functions and/or have an unusual origin.

AB - Most human T cells express the TCR α/β and either CD4 or CD8 molecules (single positive, SP); however, small numbers lack CD4 and CD8. In inbred mice, α/β CD4-CD8- (double negative, DN) T cells preferentially express certain β variable region (Vβ) families and may arise via unique developmental pathways. Increased percentages of α/β DN T cells have been identified in some human and murine autoimmune and immunodeficiency diseases. However, their contribution to disease pathology or normal immunity is unknown. To study the cell surface phenotype and TCR diversity of human α/β DN T cells, these cells were isolated from the peripheral blood of healthy adults. The proportion of α/β DN T cells expressing molecules associated with activation (HLA-DR), previous exposure to antigen (CD45RO), and cytotoxic function (CD56, CD57, and CD11b) was increased relative to SP T cells. The TCR Vβ repertoire of α/β DN T cells was different from that of α/β SP T cells, although most major gene families were present. For example, higher proportions of Vβ11, a minor gene family in peripheral blood leukocytes, were found in most α/β DN T-cell samples. In contrast to mice, no dominant Vβ family was used consistently in different human individuals. Within an individual α/β DN T cells possessed an oligoclonal TCRβ repertoire with conservation of several distinct junctional amino acid motifs with one joined to three different Vβ genes in two individuals, suggesting that these cells have undergone a selection process driven by a limited set of ligands. The possibility that they may represent, at least in part, originally SP T cells anergized by down-modulation of CD4 or CD8 must also be entertained. Overall, this study demonstrates that human peripheral blood α/β DN T cells possess unique phenotypic and TCRβ repertoire characteristics when compared with the major α/β SP T cell populations and thus may serve specialized immunologic functions and/or have an unusual origin.

UR - http://www.scopus.com/inward/record.url?scp=0027135816&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0027135816&partnerID=8YFLogxK

M3 - Article

C2 - 7505446

AN - SCOPUS:0027135816

VL - 90

SP - 11787

EP - 11791

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 - 24

ER -