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 moleculeon an APC

Linear epitops

Bcell

Tcell

C C

C C

N NN N

CH CH

CL CL

VHVHVLVL

IgA(1,2)

IgG(1,2,3,4)

IgD

IgE

IgM

CDR1

CDR2

CDR3CDR3

CDR2

CDR1

V (variable) regionVL i VH

C (constant) regionCL i CH

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

Inherited configuration of gene loci for antigen receptors

Recombination and expression of immunoglobulin genes

Mechanisms of creation of antigen receptor diversity

~100 54 67

27

461

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

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 generecombination

4.

and or and chainsc.TCR recognizes3.

proteins, polysaccharides, lipidsb.Negative selection2.

eliminates auto-reactive lymphocytesa.TCR gene recombination1.

10.____9.____8.____7.____6.____5.____4.____3.____2.____1.____g a d h c i e j b f