Abstract
The mechanisms underlying the genesis and maintenance of T cell memory remain unclear. In this study, we examined the evolution of a complex, antigen-specific T cell population during the transition from primary effector to memory T cells after Listeria monocytogenes infection. T cell populations specific for listeriolysin O (LLO)91-99, the immunodominant epitope recognized by H2-Kd-restricted T lymphocytes, were directly identified in immune spleens using tetrameric H2-Kd-epitope complexes. The T cell receptor (TCR) Vbeta repertoire of specific T cells was determined by direct, ex vivo staining with a panel of mAbs. We demonstrate that LLO91-99-specific, primary effector T cell populations have a diverse TCR Vbeta repertoire. Analyses of memory T cell populations demonstrated similar TCR diversity. Furthermore, experiments with individual mice demonstrated that primary effector and memory T cells have indistinguishable TCR repertoires. Remarkably, after reinfection with L. monocytogenes, LLO91-99-specific T cells have a narrower TCR repertoire than do primary effector or memory T cells. Thus, our studies show that the TCR repertoire of primary effector T lymphocytes is uniformly transmitted to memory T cells, whereas expansion of memory T cells is selective.
MeSH Terms
Animals
Bacterial Proteins/immunology
Bacterial Toxins
CD8-Positive T-Lymphocytes/immunology
Cells, Cultured
Flow Cytometry
Heat-Shock Proteins/immunology
Hemolysin Proteins
Histocompatibility Antigens Class I/genetics
Humans
Immunologic Memory/immunology
Interferon-gamma/metabolism
Listeria monocytogenes/immunology
Mice
Mice, Inbred BALB C
Protein Conformation
Receptors, Antigen, T-Cell/genetics,immunology
Spleen/immunology
T-Lymphocytes/immunology
Chemicals
Bacterial Proteins
Bacterial Toxins
Heat-Shock Proteins
Hemolysin Proteins
Histocompatibility Antigens Class I
Receptors, Antigen, T-Cell
Interferon-gamma
hlyA protein, Listeria monocytogenes
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Busch D H
Section of Infectious Diseases and the Section of Immunobiology, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
Pilip I
Pamer E G
References (28)
28 references, click to expand
-
Differential requirements for survival and proliferation of CD8 naïve or memory T cells.
Science. 1997 Jun 27;276(5321):2057-62
PMID: 9197272
-
Immunodominant and subdominant CTL responses to Listeria monocytogenes infection.
J Immunol. 1997 Apr 1;158(7):3366-71
PMID: 9120295
-
Epitope-dependent selection of highly restricted or diverse T cell receptor repertoires in response to persistent infection by Epstein-Barr virus.
J Exp Med. 1997 Jul 7;186(1):83-9
PMID: 9207000
-
MHC class I antigen processing of Listeria monocytogenes proteins: implications for dominant and subdominant CTL responses.
Immunol Rev. 1997 Aug;158:129-36
PMID: 9314081
-
A nonamer peptide derived from Listeria monocytogenes metalloprotease is presented to cytolytic T lymphocytes.
Infect Immun. 1997 Dec;65(12):5326-9
PMID: 9393833
-
Coordinate regulation of complex T cell populations responding to bacterial infection.
Immunity. 1998 Mar;8(3):353-62
PMID: 9529152
-
MHC class I/peptide stability: implications for immunodominance, in vitro proliferation, and diversity of responding CTL.
J Immunol. 1998 May 1;160(9):4441-8
PMID: 9574549
-
Cloned Listeria monocytogenes specific non-MHC-restricted Lyt-2+ T cells with cytolytic and protective activity.
J Immunol. 1988 May 1;140(9):3173-9
PMID: 3129513
-
T cell receptor genes in a series of class I major histocompatibility complex-restricted cytotoxic T lymphocyte clones specific for a Plasmodium berghei nonapeptide: implications for T cell allelic exclusion and antigen-specific repertoire.
J Exp Med. 1991 Dec 1;174(6):1371-83
PMID: 1836010
-
Use of peptide libraries to map the substrate specificity of a peptide-modifying enzyme: a 13 residue consensus peptide specifies biotinylation in Escherichia coli.
Biotechnology (N Y). 1993 Oct;11(10):1138-43
PMID: 7764094
-
T-cell receptors from virus-specific cytotoxic T lymphocytes recognizing a single immunodominant nine-amino-acid viral epitope show marked diversity.
J Virol. 1994 Jan;68(1):352-7
PMID: 7504738
-
The MHC class I-restricted T cell response to Sendai virus infection in C57BL/6 mice: a single immunodominant epitope elicits an extremely diverse repertoire of T cells.
Int Immunol. 1994 Nov;6(11):1767-75
PMID: 7865469
-
Antigen-specific development of primary and memory T cells in vivo.
Science. 1995 Apr 7;268(5207):106-11
PMID: 7535476
-
On the cellular basis of immunological T cell memory.
Immunity. 1995 Jan;2(1):37-43
PMID: 7600301
-
Expression in vivo of CD45RA, CD45RB and CD44 on T cell receptor-transgenic CD8+ T cells following immunization.
Eur J Immunol. 1995 Jun;25(6):1755-9
PMID: 7542202
-
Characterization of diverse primary herpes simplex virus type 1 gB-specific cytotoxic T-cell response showing a preferential V beta bias.
J Virol. 1995 Sep;69(9):5849-52
PMID: 7543591
-
Distinct phenotypes of antigen-selected CD8 T cells emerge at different stages of an in vivo immune response.
J Immunol. 1995 Oct 1;155(7):3443-52
PMID: 7561039
-
Single-cell PCR analysis of TCR repertoires selected by antigen in vivo: a high magnitude CD8 response is comprised of very few clones.
Immunity. 1996 Jan;4(1):47-55
PMID: 8574851
-
Immunological memory and protective immunity: understanding their relation.
Science. 1996 Apr 5;272(5258):54-60
PMID: 8600537
-
Visualization, characterization, and turnover of CD8+ memory T cells in virus-infected hosts.
J Exp Med. 1996 Apr 1;183(4):1367-75
PMID: 8666895
-
Memory TCR repertoires analyzed long-term reflect those selected during the primary response.
Int Immunol. 1996 Jul;8(7):1131-8
PMID: 8757958
-
Tracking antigen-specific helper T cell responses.
Curr Opin Immunol. 1996 Apr;8(2):278-84
PMID: 8725952
-
Phenotypic analysis of antigen-specific T lymphocytes.
Science. 1996 Oct 4;274(5284):94-6
PMID: 8810254
-
Epitope focusing in the primary cytotoxic T cell response to Epstein-Barr virus and its relationship to T cell memory.
J Exp Med. 1996 Nov 1;184(5):1801-13
PMID: 8920868
-
Assembly, specific binding, and crystallization of a human TCR-alphabeta with an antigenic Tax peptide from human T lymphotropic virus type 1 and the class I MHC molecule HLA-A2.
J Immunol. 1996 Dec 15;157(12):5403-10
PMID: 8955188
-
Analysis of cytotoxic T cell responses to dominant and subdominant epitopes during acute and chronic lymphocytic choriomeningitis virus infection.
J Immunol. 1996 Dec 15;157(12):5543-54
PMID: 8955205
-
Resting memory CD8+ T cells are hyperreactive to antigenic challenge in vitro.
J Exp Med. 1996 Dec 1;184(6):2141-51
PMID: 8976170
-
Immunological memory.
Curr Opin Immunol. 1997 Jun;9(3):371-9
PMID: 9203411