Definition of the HLA-A2 Restricted Peptides Recognized by Human CD8+ Effector T Cells by Flow-assisted Sorting of the CD8+ CD45RA+ CD28- T Cell Subpopulation

Overview

Journal Clin Exp Immunol

Publisher Oxford University Press

Specialty Allergy & Immunology

Date 2003 Jan 10

PMID 12519392

Citations 5

Authors

H Hohn

M Julch

H Pilch

C Kortsik

G Tully

C Neukirch

K Freitag

M Maeurer

Affiliations

Soon will be listed here.

Abstract

In response to antigenic stimulation, naive MHC-class I restricted and antigen-specific CD8+ CD45RA+ CD28+ T cells undergo clonal expansion, differentiate into CD8+ CD45RO+ memory T cells and convert to CD8+ CD45RA+ CD28- T cells displaying potent immune effector functions upon re-encounter with the nominal antigen. We show that the effector CD8+ CD45RA+ CD28- T cell subset is expanded in peripheral blood lymphocytes (PBL) from patients with human papilloma virus (HPV)+ cervical lesions as well as in PBL from patients with pulmonary tuberculosis. Flow-cytometric cell sorted CD8+ CD45RA+ CD28- and CD8+ CD45RA+ CD28- T cells were tested for recognition of HLA-A2 restricted peptides derived either from the human papillomavirus (HPV)16-E7 gene product, or from M. tuberculosis antigens. Mostly CD8+ CD45+ CD28- T cells define antigen/peptide-specific and MHC-restricted responses. These data were confirmed in PBL from patients with tuberculosis using HLA-A2 tetramer-complexes loaded with a peptide from the M. tuberculosis Ag85b antigen by flow cytometry. The sorting of this T cell subset enables to determine the fine specificity of CD8+ effector T cells without the need for in vitro manipulation.

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References

Bercovici N, Duffour M, Agrawal S, Salcedo M, Abastado J . New methods for assessing T-cell responses. Clin Diagn Lab Immunol. 2000; 7(6):859-64. PMC: 95974. DOI: 10.1128/CDLI.7.6.859-864.2000. View

Champagne P, Ogg G, King A, Knabenhans C, Ellefsen K, Nobile M . Skewed maturation of memory HIV-specific CD8 T lymphocytes. Nature. 2001; 410(6824):106-11. DOI: 10.1038/35065118. View

Weekes M, Carmichael A, Wills M, Mynard K, Sissons J . Human CD28-CD8+ T cells contain greatly expanded functional virus-specific memory CTL clones. J Immunol. 1999; 162(12):7569-77. View

Mohagheghpour N, Gammon D, Kawamura L, van Vollenhoven A, Benike C, Engleman E . CTL response to Mycobacterium tuberculosis: identification of an immunogenic epitope in the 19-kDa lipoprotein. J Immunol. 1998; 161(5):2400-6. View

Altman J, Moss P, Goulder P, Barouch D, McHeyzer-Williams M, Bell J . Phenotypic analysis of antigen-specific T lymphocytes. Science. 1996. 274: 94-96. J Immunol. 2011; 187(1):7-9. View

Westermann J, Pabst R . Lymphocyte subsets in the blood: a diagnostic window on the lymphoid system?. Immunol Today. 1990; 11(11):406-10. DOI: 10.1016/0167-5699(90)90160-b. View

Santin A, Hermonat P, Ravaggi A, Bellone S, Roman J, Jayaprabhu S . Expression of CD56 by human papillomavirus E7-specific CD8+ cytotoxic T lymphocytes correlates with increased intracellular perforin expression and enhanced cytotoxicity against HLA-A2-matched cervical tumor cells. Clin Cancer Res. 2001; 7(3 Suppl):804s-810s. View

Appay V, Dunbar P, Callan M, Klenerman P, Gillespie G, Papagno L . Memory CD8+ T cells vary in differentiation phenotype in different persistent virus infections. Nat Med. 2002; 8(4):379-85. DOI: 10.1038/nm0402-379. View

Geluk A, van Meijgaarden K, Franken K, Drijfhout J, DSouza S, Necker A . Identification of major epitopes of Mycobacterium tuberculosis AG85B that are recognized by HLA-A*0201-restricted CD8+ T cells in HLA-transgenic mice and humans. J Immunol. 2000; 165(11):6463-71. DOI: 10.4049/jimmunol.165.11.6463. View

10.

Zea A, Ochoa M, Ghosh P, Longo D, Alvord W, Valderrama L . Changes in expression of signal transduction proteins in T lymphocytes of patients with leprosy. Infect Immun. 1998; 66(2):499-504. PMC: 107934. DOI: 10.1128/IAI.66.2.499-504.1998. View

11.

Appay V, Nixon D, Donahoe S, Gillespie G, Dong T, King A . HIV-specific CD8(+) T cells produce antiviral cytokines but are impaired in cytolytic function. J Exp Med. 2000; 192(1):63-75. PMC: 1887711. DOI: 10.1084/jem.192.1.63. View

12.

Soares M, Borthwick N, Maini M, Janossy G, Salmon M, Akbar A . IL-7-dependent extrathymic expansion of CD45RA+ T cells enables preservation of a naive repertoire. J Immunol. 1998; 161(11):5909-17. View

13.

Hamann D, Baars P, Rep M, Hooibrink B, Klein M, van Lier R . Phenotypic and functional separation of memory and effector human CD8+ T cells. J Exp Med. 1997; 186(9):1407-18. PMC: 2199103. DOI: 10.1084/jem.186.9.1407. View

14.

Kono K, Ressing M, BRANDT R, Melief C, Potkul R, Andersson B . Decreased expression of signal-transducing zeta chain in peripheral T cells and natural killer cells in patients with cervical cancer. Clin Cancer Res. 1996; 2(11):1825-8. View

15.

Pittet M, Speiser D, Lienard D, Valmori D, Guillaume P, Dutoit V . Expansion and functional maturation of human tumor antigen-specific CD8+ T cells after vaccination with antigenic peptide. Clin Cancer Res. 2001; 7(3 Suppl):796s-803s. View

16.

Ahmed R, Gray D . Immunological memory and protective immunity: understanding their relation. Science. 1996; 272(5258):54-60. DOI: 10.1126/science.272.5258.54. View

17.

Chen G, Shankar P, Lange C, Valdez H, Skolnik P, Wu L . CD8 T cells specific for human immunodeficiency virus, Epstein-Barr virus, and cytomegalovirus lack molecules for homing to lymphoid sites of infection. Blood. 2001; 98(1):156-64. DOI: 10.1182/blood.v98.1.156. View

18.

Sallusto F, Lenig D, Forster R, Lipp M, Lanzavecchia A . Two subsets of memory T lymphocytes with distinct homing potentials and effector functions. Nature. 1999; 401(6754):708-12. DOI: 10.1038/44385. View

19.

McMichael A, OCallaghan C . A new look at T cells. J Exp Med. 1998; 187(9):1367-71. PMC: 2212275. DOI: 10.1084/jem.187.9.1367. View

20.

Roos M, van Lier R, Hamann D, Knol G, Verhoofstad I, van Baarle D . Changes in the composition of circulating CD8+ T cell subsets during acute epstein-barr and human immunodeficiency virus infections in humans. J Infect Dis. 2000; 182(2):451-8. DOI: 10.1086/315737. View