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J L Wung

Publications and source records attributed to J L Wung.

4 recordsLinked to original sources
PubMed1998

Polymorphism within a TCRAV family influences the repertoire through class I/II restriction.

Antibody-staining experiments have shown that closely related members of the TCRAV3 family are reciprocally selected into the CD4 or CD8 peripheral T cell subsets. This has been attributed to the individual AV3 members interacting preferentially with either MHC class I or MHC class II molecules. Single amino acid residues present in the complementarity-determining regions (CDR) CDR1alpha and CDR2alpha are important in determining MHC class specificity. We have now extended these observations to survey the expressed repertoire of the AV3 family in C57BL/6 mice. Three of the four expressed AV3 members are preferentially selected into the CD4+ subset of T cells. These share the same amino acid residue in both CDR1alpha and CDR2alpha that differ from the only CD8-skewed member. Preferential expression of an individual AV3 is not caused by other endogenous alpha- or beta-chains, by any conserved CDR3 sequence, or by the usage of TCRAJ regions. This study shows that residues in the CDR1 and CDR2 regions are primary determinants for MHC class discrimination and suggests that polymorphism found within a TCRAV family has an important effect on the overall shaping of the T cell repertoire.

Amino Acid Sequence↗
PubMed1997

Selection of phage-displayed superantigen by binding to cell-surface MHC class II.

We have expressed the superantigen staphylococcal enterotoxin A (SEA) on the surface of bacteriophage as a fusion with the gene VIII protein (gVIIIp). This phage-displayed superantigen retains the properties inherent in the natural protein. It binds to MHC class II and activates T-cells bearing appropriate V beta regions. A flexible 5-amino acid linker sequence between the SEA molecule and the phage coat protein improved the production of functional phage-displayed SEA. Binding to MHC class II-expressing cells effectively selected SEA-phage from non-SEA-phage background. This indicates that this will be an effective method for selecting new specificities of superantigen from libraries of SEA mutants and for cloning of novel superantigens.

Amino Acid Sequence↗
PubMed1996

T-cell-receptor affinity and thymocyte positive selection.

Development of thymocytes involves two distinct outcomes resulting from superficially similar events. Recognition by thymocytes of major histocompatibility complex (MHC) proteins plus peptides leads to their rescue from apoptosis (positive selection), and recognition of antigenic peptide induces cell death (negative selection). Antigen analogues, and sometimes low concentrations of antigenic peptide, induce positive selection; such analogues are often antagonists of mature T-cell clones. Various models seek to explain how recognition of different peptide/MHC complexes leads to such different outcomes: quantitative models relate response to the affinity, avidity or kinetics of T-cell-antigen receptor (TCR) binding, whereas qualitative models require conformational or spatial changes in the TCR or associated molecules to modulate signal transduction. We have used surface plasmon resonance to measure the kinetics of TCR interactions with positively and negatively selecting ligands to distinguish between these models, and find that affinity correlates to the outcome of selection. A 'window' of affinity resulting in positive selection extends over a 1-log range starting threefold below the affinity for negative selection.

Amino Acid Sequence↗