The latest study from the Jill Roberts Institute, "The neuropeptide neuromedin U stimulates innate lymphoid cells and type 2 inflammation," was published on September 6 in Nature. To read more, click here.     Dr. Gregory Sonnenberg wins inaugural award from the Society for Mucosal Immunology. To read more, click here.  The Kenneth Rainin Foundation awarded Dr. Iliyan Iliev and colleagues from Mount Sinai a $250,000 Synergy Award to examine the composition of the fungal community in babies born to mothers with inflammatory bowel disease. To read more, click here. Dr. Randy Longman received the Irma T. Hirschl Career Scientist Award and the New York Crohn’s Foundation Award.    

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Alteration at a single amino acid residue in the T cell receptor alpha chain complementarity determining region 2 changes the differentiation of naive CD4 T cells in response to antigen from T helper cell type 1 (Th1) to Th2.

TitleAlteration at a single amino acid residue in the T cell receptor alpha chain complementarity determining region 2 changes the differentiation of naive CD4 T cells in response to antigen from T helper cell type 1 (Th1) to Th2.
Publication TypeJournal Article
Year of Publication2000
AuthorsBlander, JM, Sant'Angelo, DB, Bottomly, K, Janeway, CA
JournalJ Exp Med
Volume191
Issue12
Pagination2065-74
Date Published2000 Jun 19
ISSN0022-1007
KeywordsAnimals, CD4-Positive T-Lymphocytes, Cell Differentiation, Genes, T-Cell Receptor alpha, Immunity, Cellular, Interferon-gamma, Interleukin-4, Major Histocompatibility Complex, Mice, Mice, Mutant Strains, Mice, Transgenic, Mutation, Peptides, Receptors, Antigen, T-Cell, alpha-beta, Th1 Cells, Th2 Cells
Abstract

To study whether changes in the structure of a T cell receptor (TCR) at a single peptide-contacting residue could affect T cell priming with antigenic peptide, we made transgenic mice with a point mutation in the TCR alpha chain of the D10.G4.1 (D10) TCR and bred them to D10 beta chain transgenic mice. The mutation consisted of a leucine to serine substitution at position 51 (L51S), which we had already established contacted the second amino acid of the peptide such that the response to the reference peptide was reduced by approximately 100-fold. A mutation in the reference peptide CA134-146 (CA-WT) from the arginine at peptide position 2 to glycine (R2G) restored full response to this altered TCR. When we examined in vitro priming of naive CD4 T cells, we observed that the response to doses of CA-WT that induced T helper cell type 1 (Th1) responses in naive CD4 T cells from mice transgenic for the D10 TCR gave only Th2 responses in naive CD4 T cells derived from the L51S. However, when we primed the same T cells with the R2G peptide, we observed Th1 priming in both D10 and L51S naive CD4 T cells. We conclude from these data that a mutation in the TCR at a key position that contacts major histocompatibility complex-bound peptide is associated with a shift in T cell differentiation from Th1 to Th2.

Alternate JournalJ. Exp. Med.
PubMed ID10859331
PubMed Central IDPMC2193209
Grant ListR01 AI014579 / AI / NIAID NIH HHS / United States
R37 AI014579 / AI / NIAID NIH HHS / United States
AI14579-22 / AI / NIAID NIH HHS / United States