T Cells & T Cell Receptors PDF

T cells & T cell receptors Learning Objectives On completion of this session you should be able to 1) Describe the structure of the T cell receptors (TCRs). 2) Explain how TCRs recognise and bind to peptide-MHC complexes. 3) Comprehend TCR gene rearrangement and diversity. Introduction 1) Pr...

T cells & T cell receptors Learning Objectives On completion of this session you should be able to 1) Describe the structure of the T cell receptors (TCRs). 2) Explain how TCRs recognise and bind to peptide-MHC complexes. 3) Comprehend TCR gene rearrangement and diversity. Introduction 1) Provide cell mediated immunity of adaptive response 2) Different populations of effector T cells: cytotoxic (CD 8+ Tc) helper (CD 4+ TH1, TH2, TFH) 3) Four principal effector functions: induce cell death - Tc activate macrophages/inflammation - TH1 anti-parasitic response – TH2 mediate B cell activation - TFH 4) Activity is mediated through interactions between cell surface proteins on T cells (TCR) and target cells (MHC - peptide) T Cell Receptor 1) Protein complex of TCR and associated proteins 2) TCR comprises 2 polypeptide chains - or  3) TCRs are most common 4) Associated CD3 proteins provide signalling function 5) Co-receptors are required for ligand recognition - CD4 or CD8 6) Two main populations of T cell exist based on co-receptor expression -> CD 4+ and CD 8+ T Cell Receptor ITAM = Immunoreceptor Tyrosine-based activation motif T Cell Receptor 1) TCR heterodimers are similar to immunoglobulins 2) Therefore they are classified in immunoglobulin superfamily 3) Resembles Fab fragment T Cell Receptor Ligands 1) MHC proteins + antigenic (non-self) peptide 2) 2 classes of MHC protein -> Class I and Class II 3) Class I on surface of all nucleated body cells 4) Class II on surface of antigen presenting cells (APCs) T Cell Receptor Ligands 1) T cells MUST distinguish between peptides derived from self and non-self proteins 2) CD8 co-receptors recognise invariant parts on MHC Class I proteins 3) CD4 co-receptors recognise invariant parts on MHC Class II proteins T Cell Receptor Ligand T Cell Receptor vs B Cell Receptor 1) T cell receptor is only membrane bound 2) Antigen binding of T cell receptor is weaker than that of antibodies 3) Antigen recognised by T cells is not antigen alone but antigen associated with MHC molecules Generation of TCR diversity (a lot like Ig) 1) Multiple germ-line gene segments Combinatorial V-(D)-J joining Junctional flexibility P-region nucleotide addition N-region nucleotide addition Combinatorial association of light and heavy chains 2) However, there is no somatic mutation with TCR May be to ensure that after thymic selection, the TCR doesn’t change to cause self-reactive T cells 1) Allogeneic – genetically different individuals of same species 2) Alloreactivity of T cells is puzzling: 3) Evidence supports that T cells can only respond to antigen+MHC 4) However, T cells can recognise a foreign MHC molecule alone - As with transplants Summary 1. T cell receptors (TCRs) are integral to the adaptive immune system, recognising peptide antigens presented by major histocompatibility complex (MHC) molecules. 2. Structurally, TCRs are composed of alpha and beta (or gamma and delta) chains, with variable regions that interact specifically with peptide-MHC complexes. 3. The diversity of TCRs is essential for the immune system's ability to recognise a wide range of antigens.