An MHC interaction site maps to the amino-terminal half of the T cell receptor α chain variable domain

Hong, Sangjin; Chelouche, Adina; Lin, Rong‐Hwa; Shaywitz, David A.; Braunstein, Ned; Glimcher, Laurie H.; Janeway, Charles A.

doi:10.1016/0092-8674(92)90618-m

Cited by 91 publications

(69 citation statements)

References 65 publications

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“…The D10 T cell clone also responds to a wide array of non-self MHC class II alleles including I-A b,q,v,p&d (36,37). D10 T cells do not proliferate in response to APCs expressing I-A f,r,s&u (38,39). Monoclonal anti-MHC class II antibodies block stimulation of D10 T cells by these various ligands.…”

Section: Resultsmentioning

confidence: 99%

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Negative selection of thymocytes expressing the D10 TCR

Sant’Angelo

Janeway

2002

Proc. Natl. Acad. Sci. U.S.A.

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We have analyzed the patterns of positive and negative selection of thymocytes expressing the T cell antigen receptor (TCR) from the D10.G4.1 T cell clone. This TCR confers reactivity to several non-self MHC class II alleles with a remarkably broad range of avidities. Therefore, negative selection can be studied when induced by high-, intermediate-, or low-avidity interactions with endogenous peptide-MHC complexes, all within the same TCR transgenic system. These data directly demonstrate that MHC class II-peptide ligands that fail to activate mature T cells can promote negative selection of immature thymocytes. Additionally, we show that negative selection of thymocytes can occur at two distinct ''time points'' during development depending on the avidity of the TCR for the MHC-peptide complex. Finally, we show that the selfpeptide repertoire plays a significant role in selection because alteration of the self-peptide repertoire by disruption of the H2-Ma gene drastically alters selection of D10 TCR-expressing thymocytes.

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Section: Resultsmentioning

confidence: 99%

“…The D10 TCR confers reactivity to a wide range of non-self MHC class II molecules (36,38,39); therefore, it provides a unique system to study intrathymic negative selection mediated by endogenous MHC-peptide complexes. Negative selection of thymocytes expressing transgenic TCRs has been observed in several different systems (refs.…”

Section: Discussionmentioning

confidence: 99%

Negative selection of thymocytes expressing the D10 TCR

Sant’Angelo

Janeway

2002

Proc. Natl. Acad. Sci. U.S.A.

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“…Peptide plus MHC recognition by c~/B T cells is mainly mediated by the V(D)J junctional CDR3 (25,26), and the role of TCK-y/IS junctional sequences in the specificity of antigen recognition has been recently stressed (27). In the present work, we have shown that V81-J81junctions, while displaying the extensive alterations of germline sequences that are characteristic of post fetal stages (14), are not randomly represented among PBL V/$1 + cells in a large fraction of healthy donors.…”

Section: Discussionmentioning

confidence: 99%

Peripheral selection of V delta 1+ cells with restricted T cell receptor delta gene junctional repertoire in the peripheral blood of healthy donors.

Beldjord

Macintyre

et al. 1993

The Journal of Experimental Medicine

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SummaryTo characterize the T cell receptor (TCR) repertoire expressed by the V/~l + 3"//~ T cell population, we have studied the V#l-J/~l junctional sequences from peripheral blood samples of healthy donors. We show that, surprisingly, this repertoire is restricted in most healthy adults, with a donor-specific and relatively stable pattern, whereas this repertoire remains unrestricted in infants, and is similar to that of thymocytes. These data contrast with the general assumption that the junctional repertoire of V~I § 3'/# T cells is extensive, and strongly suggest that peripheral recruitment of V/~I + cells bearing particular TCR occurs in humans during the postnatal stage.

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“…The conclusions from these studies (Hong et al, 1992;Portoles et al, 1989) are: 1 -Single Vdomains recognize allele-specific determinants either restrictively (P-dependent) or alloreactively (P-independent). 2 -Vβ8.2 recognizes the allele-specific determinant on , whereas Vα2 recognizes the alloallele-specific determinant on .…”

Section: The Biological Studymentioning

confidence: 99%

“…The D10 TCR specific for A k -Pcon has been extensively characterized (Table I) by analyzing the response of a hybridoma to various complemented pairs of Aα and Aβ alleles (Hong et al, 1992;Portoles et al, 1989). The D10 TCR is restricted to A k and alloreactive among others to the allele A b .…”

Section: The Biological Studymentioning

confidence: 99%

What does the T-cell receptor recognize when it docks on an MHC-encoded restricting element?

Cohn

2008

Molecular Immunology

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The postulate is analyzed that single V-gene segments encode recognition of the allele-specific determinants (a) required for the restrictive response of the αβTCR to peptide. The consequence of this is that the positively selected V-domain, Vα or Vβ, engages an allele-specific determinant (a) on one subunit or domain of the MHC-encoded restricting element. The entrained V-domain docks on an invariant determinant (i) on the complementing subunit or domain. Consequently, each functional V-domain expresses an anti-a site and an anti-i site, and all subunits or domains of MHCencoded restricting elements express an a-and i-determinant.The evidence, both biological and structural, discussed here strongly support this postulate which has far reaching consequences.The goal of this commentary is to analyze the data that are necessary and sufficient to establish a postulate of the Tritope Model, namely that the V-gene segments, Vα and Vβ, act as an single pool specifying recognition of the allele-specific determinants expressed on the MHC-encoded restricting elements of the species. Aspects of this postulate will also be discussed.This version was revised to incorporate the criticisms of reviewers who also requested that I discuss additional data. As a compromise, those data which are believed to be incompatible with my argument, are analyzed.

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An MHC interaction site maps to the amino-terminal half of the T cell receptor α chain variable domain

Cited by 91 publications

References 65 publications

Negative selection of thymocytes expressing the D10 TCR

Negative selection of thymocytes expressing the D10 TCR

Peripheral selection of V delta 1+ cells with restricted T cell receptor delta gene junctional repertoire in the peripheral blood of healthy donors.

What does the T-cell receptor recognize when it docks on an MHC-encoded restricting element?

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