Core B will provide a variety of IVIHC and TCR reagents, and will perform experiments using these reagents, in support of the research projects. Routine services that will be provided include production of purified recombinant MHC and TCR proteins for tetramer staining and affinity measurements, testing and quality control of tetramer reagents, biophysical measurements of MHC-peptide and MHC-TCR binding affinity and kinetics, and structural characterization of MHC-peptide complexes. This core will also be partly developmental. Developmental services that will be provided include production of MHC heterodimers for characterization of T cell cross reactivity, and creation of improved reagents for analyzing class ll-restricted CD4 T cells based on current understanding of MHC II peptide interactions.
The specific aims of this work are to generate bifunctional MHC dimers to detect cross-reactive T cells, to develop class II MHC tetrarner technology for l-A(b), to measure binding affinity and kinetics for MHC-TCR pairs, and to provide class I MHC tetramer reagents not available from the NIH tetramer facility. Services provided by core B will be used by Project 1 (Swain), Project 2 (Welsh), Project 3 (Tsuda), and Project 4 (Selin), and also by Core C (Huseby),
The MHC and TCR core facility (Core B) will provide centralized protein biochemistry and biophysics services for the research groups studying the immunological aspects of the CD4+ response to viruses.
|Che, Jenny W; Kraft, Anke R M; Selin, Liisa K et al. (2015) Regulatory T cells resist virus infection-induced apoptosis. J Virol 89:2112-20|
|Stepanek, Ondrej; Prabhakar, Arvind S; Osswald, Celine et al. (2014) Coreceptor scanning by the T cell receptor provides a mechanism for T cell tolerance. Cell 159:333-45|
|McKinstry, K Kai; Strutt, Tara M; Bautista, Bianca et al. (2014) Effector CD4 T-cell transition to memory requires late cognate interactions that induce autocrine IL-2. Nat Commun 5:5377|
|Stadinski, Brian D; Huseby, Eric S (2014) Identifying environmental antigens that activate myelin-specific T cells. Trends Immunol 35:231-2|
|Keck, Simone; Schmaler, Mathias; Ganter, Stefan et al. (2014) Antigen affinity and antigen dose exert distinct influences on CD4 T-cell differentiation. Proc Natl Acad Sci U S A 111:14852-7|
|Daniels, Keith A; Hatfield, Steven D; Welsh, Raymond M et al. (2014) MHC basis of T cell-dependent heterologous immunity to arenaviruses. Virology 464-465:213-7|
|Becerra, Aniuska; Gibson, Laura; Stern, Lawrence J et al. (2014) Immune response to HHV-6 and implications for immunotherapy. Curr Opin Virol 9:154-61|