Molecular basis of TCR selectivity, cross-reactivity, and allelic discrimination by a bacterial superantigen: integrative functional and energetic mapping of the SpeC-Vbeta2.1 molecular interface.

Molecular basis of TCR selectivity, cross-reactivity, and allelic discrimination by a bacterial superantigen: integrative functional and energetic mapping of the SpeC-Vbeta2.1 molecular interface. Research Abstract Details 

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Molecular basis of TCR selectivity, cross-reactivity, and allelic discrimination by a bacterial superantigen: integrative functional and energetic mapping of the SpeC-Vbeta2.1 molecular interface. Abstract Text:

A K M Nur-ur Rahman,Christine A Herfst,Beenu Moza,Stephanie R Shames,Luan A Chau,Clara Bueno, Madrenas,Eric J Sundberg,John K McCormick,

Superantigens activate large fractions of T cells through unconventional interactions with both TCR beta-chain V domains (Vbetas) and MHC class II molecules. The bacterial superantigen streptococcal pyrogenic exotoxin C (SpeC) primarily stimulates human Vbeta2(+) T cells. Herein, we have analyzed the SpeC-Vbeta2.1 interaction by mutating all SpeC residues that make contact with Vbeta2.1 and have determined the energetic and functional consequences of these mutations. Our comprehensive approach, including mutagenesis, functional readouts from both bulk T cell populations, and an engineered Vbeta2.1(+) Jurkat T cell, as well as surface plasmon resonance binding analysis, has defined the SpeC "functional epitope" for TCR engagement. Although only two SpeC residues (Tyr(15) and Arg(181)) are critical for activation of virtually all human CD3(+) T cells, a larger cluster of four hot spot residues are required for interaction with Vbeta2.1. Three of these residues (Tyr(15), Phe(75), and Arg(181)) concentrate their binding energy on the CDR2 loop residue Ser(52a), a noncanonical residue insertion found only in Vbeta2 and Vbeta4 chains. Plasticity of this loop is important for recognition by SpeC. Although SpeC interacts with the Vbeta2.1 hypervariable CDR3 loop, our data indicate these contacts have little to no influence on the functional interaction with Vbeta2.1. These studies also provide a molecular basis for selectivity and cross-reactivity of SpeC-TCR recognition and reveal a degree of fine specificity in these interactions, whereby certain SpeC mutants are capable of distinguishing between different alleles of the same Vbeta domain subfamily.

Molecular basis of TCR selectivity, cross-reactivity, and allelic discrimination by a bacterial superantigen: integrative functional and energetic mapping of the SpeC-Vbeta2.1 molecular interface. Publishing Authors By Initials

AK Rahman,CA Herfst,B Moza,SR Shames,LA Chau,C Bueno,J Madrenas,EJ Sundberg,JK McCormick,

For similar biological phenomena, cell phenomena, and immunity: immunity: t-cell antigen receptor specificity research abstracts see: biological phenomena, cell phenomena, and immunity: immunity: t-cell antigen receptor specificity research

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Molecular basis of TCR selectivity, cross-reactivity, and allelic discrimination by a bacterial superantigen: integrative functional and energetic mapping of the SpeC-Vbeta2.1 molecular interface. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Journal of immunology (Baltimore, Md. : 1950)

VOLUME: 177

Page Numbers: 8595-603

Journal Abbreviation: J. Immunol.

ISSN: 0022-1767

DAY: 15

MONTH: Dec

YEAR: 2006

Molecular basis of TCR selectivity, cross-reactivity, and allelic discrimination by a bacterial superantigen: integrative functional and energetic mapping of the SpeC-Vbeta2.1 molecular interface. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 2985117

Molecular basis of TCR selectivity, cross-reactivity, and allelic discrimination by a bacterial superantigen: integrative functional and energetic mapping of the SpeC-Vbeta2.1 molecular interface. Keywords Mesh Terms:

KEYWORDS: T-Cell Antigen Receptor Specificity

MESH TERMS: immunology

Chemical & Substance for Abstract: Molecular basis of TCR selectivity, cross-reactivity, and allelic discrimination by a bacterial superantigen: integrative functional and energetic mapping of the SpeC-Vbeta2.1 molecular interface. Information

Substance Name: erythrogenic toxin

Registry Number: 0

Grant and Affiliation Information for Molecular basis of TCR selectivity, cross-reactivity, and allelic discrimination by a bacterial superantigen: integrative functional and energetic mapping of the SpeC-Vbeta2.1 molecular interface.

AFFILIATION: Lawson Health Research Institute.

Country: United States

AGENCY: United States NIAID

GRANT: AI 55882

ACRONYM: AI

MEDLINETA: J Immunol

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