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Titolo:
Negative selection during the peripheral immune response to antigen
Autore:
Anderton, SM; Radu, CG; Lowrey, PA; Ward, ES; Wraith, DC;
Indirizzi:
Univ Bristol, Sch Med Sci, Dept Pathol & Microbiol, Bristol BS8 1TD, Avon,England Univ Bristol Bristol Avon England BS8 1TD , Bristol BS8 1TD, Avon,England Univ Texas, SW Med Ctr, Ctr Canc Immunobiol, Dallas, TX 75235 USA Univ Texas Dallas TX USA 75235 Ctr Canc Immunobiol, Dallas, TX 75235 USA
Titolo Testata:
JOURNAL OF EXPERIMENTAL MEDICINE
fascicolo: 1, volume: 193, anno: 2001,
pagine: 1 - 11
SICI:
0022-1007(20010101)193:1<1:NSDTPI>2.0.ZU;2-5
Fonte:
ISI
Lingua:
ENG
Soggetto:
MYELIN BASIC-PROTEIN; T-CELL-RECEPTOR; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; MAJOR HISTOCOMPATIBILITY COMPLEX; CLASS-II MHC; QUANTITATIVE-ANALYSIS; POSITIVE SELECTION; PEPTIDE COMPLEXES; MOLECULAR MIMICRY; SELF-ANTIGEN;
Keywords:
T cells; repertoire selection; autoimmunity; encephalomyelitis; apoptosis;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
65
Recensione:
Indirizzi per estratti:
Indirizzo: Anderton, SM Univ Edinburgh, Inst Cell Anim & Populat Biol, Ashworth Labs,Kings Bldg,WMains Rd, Edinburgh EH9 3JT, Midlothian, Scotland Univ Edinburgh Kings Bldg,W Mains Rd Edinburgh Midlothian Scotland EH9 3JT
Citazione:
S.M. Anderton et al., "Negative selection during the peripheral immune response to antigen", J EXP MED, 193(1), 2001, pp. 1-11

Abstract

Thymic selection depends oil positive and negative selective mechanisms based on the avidity of T cell interaction with antigen-major histocompatibility complex complexes. However, peripheral mechanisms for the recruitment and clonal expansion of the responding T cell repertoire remain obscure. Here we provide evidence for an avidity-based model of peripheral T cell clonal expansion in response to antigenic challenge. We have used the encephalitogenic, H-2 A(u)-restricted, acetylated NH2-tenuinal nonameric peptide (Acl-9) epitope from myelin basic protein as our model antigen. Peptide analogues were generated that varied in antigenic strength (as assessed by in vitro assay) based on differences in their binding affinity for A(u). In vivo, these analogues elicited distinct repertoires of T cells that displayed marked differences in antigen sensitivity. Immunization with the weakest (wild-type) antigen expanded the high affinity T cells required to induce encephalomyelitis. In contrast, immunization with strongly antigenic analogues led to the elimination of T cells bearing high affinity T cell receptors by apoptosis, thereby preventing disease development. Moreover, the T cell repertoire was consistently tuned to respond to the immunizing antigen with thesame activation threshold. This tuning mechanism provides a peripheral control against the expansion of autoreactive T cells and has implications forimmunotherapy and vaccine design.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 24/11/20 alle ore 14:32:51