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In a small multideterminant peptide, each determinant is recognized by a different V beta gene segment
N K Nanda1, K K Arzoo, E E Sercarz
1Department of Microbiology and Molecular Genetics, University of California, Los Angeles 90024.
The Journal of Experimental Medicine
|July 1, 1992
Summary
T cell receptor (TCR) V beta gene usage significantly impacts immune responses. Mice lacking specific V beta genes show altered responses to sperm whale myoglobin peptide 110-121, highlighting constraints in T cell recognition.
Area of Science:
- Immunology
- T cell receptor (TCR) biology
- Molecular immunology
Background:
- The T cell receptor (TCR) repertoire diversity is vast, enabling responses to numerous antigens.
- Studies on V(a) beta mice, which lack specific TCR V beta gene segments, were expected to still mount antigen-specific T cell responses.
- Previous work showed Vb beta mice (wild-type TCR V beta repertoire) respond to myoglobin peptide 110-121 using specific V beta 8.2 and V beta 8.1 T cells restricted by MHC molecules.
Purpose of the Study:
- To investigate the antigen-specific T cell response in V(a) beta mice lacking TCR V beta 8 gene family members.
- To determine if the apparent plasticity in I-A(d)-restricted responses in V(a) beta mice reflects distinct determinant recognition.
- To elucidate the association between TCR V beta usage and T cell specificity for different determinants within a single peptide.
Main Methods:
- Generation and analysis of T cell hybridomas from V(a) beta and Vb beta mice.
- Characterization of T cell responses to sperm whale myoglobin peptide 110-121 and its determinants.
- Mapping of T cell receptor (TCR) specificity to distinct peptide regions and major histocompatibility complex (MHC) restriction.
Main Results:
- V(a) beta mice, lacking TCR V beta 8, responded only with I-A(d)-restricted T cells, unlike Vb beta mice.
- T cell hybrids from V(a) beta and Vb beta mice recognized distinct determinants within peptide 110-121.
- V(a) beta T cells recognized an NH2-terminal determinant (110-118, requiring Ala-110), while Vb beta T cells recognized a COOH-terminal determinant (112-118, requiring residue 118).
Conclusions:
- V(a) beta mice cannot recognize the dominant MHC-restricted determinants of peptide 110-121, responding instead to a less dominant NH2-terminal determinant.
- There is a strict association between specific T cell receptor V beta usage and the recognition of particular peptide determinants.
- The observed specificities suggest significant constraints in V beta expression, rather than plasticity, in T cell recognition of individual determinants.