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Outline of Lectures 08 and 09

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Ryerson University
BLG 307
Clare Chua

Outline of Lectures 08 and 09 Antigen Recognition by T Cells, I and II I. Importance of T lymphocytes - Both T and B cells are needed to generate an Ab response (Claman reconstitution expt) - Helper T cells activate B cells to produce Ab - Cytotoxic T cells are the other type of T cell, which actively kill other cells - T cells are clonally selected via Ag recognition by the T cell receptor - T cell Ag recognition is similar (e.g. TCR, Ig are homologous) to that in B cells, but distinct in mechanism - T cells develop in the thymus (this is the principle function of this organ) II. T Cells Recognize Ag by a Unique Mechanism - T cells recognize linear 9-10 aa peptide sequences - T cells only recognize Ag’s presented on the surfaces of other cells (APC’s such as dendritic cells or macrophages) - MHC restriction: the MHC allele expressed on the APC must be correct to stimulate T cells III. Major Histocompatibility Complex A) Discovery of the MHC - discovered by mapping cell surface antigen responsible for tumor graft rejection - the surface antigen is the MHC, recipient and donor must have matching MHC’s for graft to be accepted - the MHC is called H-2 in mice and HLA in humans B) The MHC locus encodes three classes of molecules MHC Class I - Dimer of αchain and β2m (not in locus) - Three types, HLA A, B, C (in mouse, H-2K, -2D, -2L) - Expressed on all cell surfaces except neurons and RBC - Special subclass Ib is nonpolymorphic and tissue specific, related to bacterial pathogen response MHC Class II - Heterodimer of αand β chains - Three types DP, DQ, DR (in mouse I-A, I-E) - Only expressed on APC’s MHC Class III - related to complement and cytokines, irrelevant to this topic C) MHC genes are highly polymorphic - polymorphism in HLA genes for both class I and II is “balanced” - nomenclature: HLA A*(allele #) (in mouse, superscript is allele type) - most variation is localized to Ag binding domains (α α1i2 class I, α β1 1 in class II) D) MHC restriction is mediated by specific recognition by the TCR - T cells are activated only if APC expresses the correct MHC - Can test which MHC is responsible directly (correlate genotypes with response) or by specific blocking with antibodies - Only one TCR needed to recogn
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