1. Antigen recognition in adaptive immunity Mechanism of diversity of antigen receptors Maturation and selection of B lymphocytes Maturation and selection of T lymphocytes

3. Cells within one clone display only one type of receptor specific for a certain ligand Cells display several types of receptor and each of them is specific for a certain ligand

4. Antigen receptors on lymphocytes Antigens: proteins, polysaccharides, lipids, nucleic acids, small molecules Conformational and linear epitops Complex of peptide-MHC molecule on an APC Linear epitops B cell T cell

5. CC CC NN NN

6. CHCH CHCH CLCL CLCL VHVH VHVH VLVL VLVL                     IgA (1,2) IgG (1,2,3,4) IgD IgE IgM CDR1 CDR2 CDR3 CDR2 CDR1 V (variable) region V L i V H C (constant) region C L i C H Isotype

7. Antibodies structure function

8. T-cell receptor for antigen (TCR) structure

10. Lymphocyte maturation

11. Susumu Tonegawa "for his discovery of the genetic principle for generation of antibody diversity" The Nobel Prize in Physiology or Medicine 1987

12. Inherited configuration of gene loci for antigen receptors

13. Nasleđena konfiguracija genskih lokusa za antigenske receptore

14. Recombination and expression of immunoglobulin genes

15. Mechanisms of creation of antigen receptor diversity ~100 54 67 27 461

16. Every day 10 9 lymphocytes with 10 7 various specificities are generated (young)

17. Phases of B-cell maturation and selection

22. T-cell maturation in thymus

24. Faze u sazrevanju i selekciji T-limfocita

25. enables survival of useful lymphocytesj.Receptors of different clones of B cells have different 10. two identical heavy and two identical light chains i.Antibody can recognize9. provides antibody diversityh.Positive selection8. occurs only in thymusg.Different isotypes have the same7. variable regions of heavy and light chains f.Antibody has6. constant region of heavy chainse.TCR consists of5. peptides within MHC moleculed.Immunoglobulin gene recombination 4.  and  or  and  chains c.TCR recognizes3. proteins, polysaccharides, lipidsb.Negative selection2. eliminates auto-reactive lymphocytesa.TCR gene recombination1. 10.____9.____8.____7.____6.____5.____4.____3.____2.____1.____ gadhciejbf