Antigen recognition in adaptive immunity Mechanism of diversity of antigen receptors Maturation and selection of B lymphocytes Maturation and selection of T lymphocytes
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
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
CC CC NN NN
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
Antibodies structure function
T-cell receptor for antigen (TCR) structure
Lymphocyte maturation
Susumu Tonegawa "for his discovery of the genetic principle for generation of antibody diversity" The Nobel Prize in Physiology or Medicine 1987
Inherited configuration of gene loci for antigen receptors
Nasleđena konfiguracija genskih lokusa za antigenske receptore
Recombination and expression of immunoglobulin genes
Mechanisms of creation of antigen receptor diversity ~
Every day 10 9 lymphocytes with 10 7 various specificities are generated (young)
Phases of B-cell maturation and selection
T-cell maturation in thymus
Faze u sazrevanju i selekciji T-limfocita
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