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Antigen recognition in adaptive immunity Mechanism of diversity of antigen receptors Maturation and selection of B lymphocytes Maturation and selection of T lymphocytes Cells display several types of receptor and each of them is specific for a certain ligand Cells within one clone display only one type of receptor specific for a certain ligand Antigen receptors on lymphocytes B T cell cell Antigens: proteins, polysaccharides, lipids, nucleic acids, small molecules Conformational and linear epitops Complex of peptide-MHC molecule on an APC Linear epitops N N N C C C C N VH VL VH VL CDR1 CDR1 CDR2 CDR2 CDR3 CDR3 CL Isotype a (a1 a2) IgA(1,2) g (g1 g2 g3 g4) IgG(1,2,3,4) V (variable) region VL i VH C (constant) region CL i CH k l CL CH CH d e IgD m IgM IgE Antibodies • structure • function T-cell receptor for antigen (TCR) structure Lymphocyte maturation The Nobel Prize in Physiology or Medicine 1987 "for his discovery of the genetic principle for generation of antibody diversity" Susumu Tonegawa Inherited configuration of gene loci for antigen receptors Nasleđena konfiguracija genskih lokusa za antigenske receptore Recombination and expression of immunoglobulin genes ~100 Mechanisms of creation of antigen receptor diversity 54 67 27 61 4 Every day 109 lymphocytes with 107 various specificities are generated (young) Phases of B-cell maturation and selection Phases of B-cell maturation and selection Phases of B-cell maturation and selection Phases of B-cell maturation and selection Phases of B-cell maturation and selection T-cell maturation in thymus T-cell maturation in thymus Faze u sazrevanju i selekciji T-limfocita 1. TCR gene recombination a. eliminates auto-reactive lymphocytes 2. Negative selection b. proteins, polysaccharides, lipids 3. TCR recognizes c. a and b, or g and d chains 4. Immunoglobulin gene recombination d. peptides within MHC molecule 5. TCR consists of e. constant region of heavy chains 6. Antibody has f. 7. Different isotypes have the same g. variable regions of heavy and light chains occurs only in thymus 8. Positive selection h. provides antibody diversity 9. Antibody can recognize i. two identical heavy and two identical light chains enables survival of useful lymphocytes 10. Receptors of different clones of B cells have different j. g a d 4.____ h 5.____ c 6.____ i 7.____ e 8.____ j 9.____ b 10.____ f 1.____ 2.____ 3.____