antigen receptors of lymphocytes. recognition: molecular patterns recognition : molecular details...

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Antigen Receptors of Lymphocytes

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Page 1: Antigen Receptors of Lymphocytes. Recognition: molecular patterns Recognition : molecular details (antigenic determinants) Innate immunity Aquired immunity

Antigen Receptors of Lymphocytes

Page 2: Antigen Receptors of Lymphocytes. Recognition: molecular patterns Recognition : molecular details (antigenic determinants) Innate immunity Aquired immunity

Recognition: molecular patterns

Recognition : molecular details (antigenic determinants)

Innate immunity

Aquired immunity (T i B lymphocytes)

Genes: functional, germline encoded

Genes: functional after DNA recombination

Receptors for recognition

Distribution: non-clonal distribution (same receptor on all cells within a cell line and even on the different lineages)

Presence: multiple copies of the same receptor

Distribution: clonal (cells within one clone exhibites receptor of the same specificity)

Presence: multiple copies of different receptors

Page 3: Antigen Receptors of Lymphocytes. Recognition: molecular patterns Recognition : molecular details (antigenic determinants) Innate immunity Aquired immunity

Antigen Receptors of Lymphocytes - Similiarity

On the lymphocyte membrane

Membrane Ig Antigen presenting cell

Antibody (Immunoglobulin) T-cell receptor(TCR)

Page 4: Antigen Receptors of Lymphocytes. Recognition: molecular patterns Recognition : molecular details (antigenic determinants) Innate immunity Aquired immunity

Antigen Receptors of Lymphocytes - Similiarity

On the lymphocyte membraneMembers of the immunoglobulin superfamily (domain structure)

Ig domains

Page 5: Antigen Receptors of Lymphocytes. Recognition: molecular patterns Recognition : molecular details (antigenic determinants) Innate immunity Aquired immunity

Antigen Receptors of Lymphocytes - Similiarity

On the lymphocyte membraneMembers of the immunoglobulin superfamily (domain structure)Two different chains

Page 6: Antigen Receptors of Lymphocytes. Recognition: molecular patterns Recognition : molecular details (antigenic determinants) Innate immunity Aquired immunity

Antigen Receptors of Lymphocytes - Similiarity

On the lymphocyte membraneMembers of the immunoglobulin superfamily (domain structure)Two different chainsVariable domains in contact with antigen (encoded by recombined DNA)

Page 7: Antigen Receptors of Lymphocytes. Recognition: molecular patterns Recognition : molecular details (antigenic determinants) Innate immunity Aquired immunity

Antigen Receptors of Lymphocytes - Similiarity

On the lymphocyte membraneMembers of the immunoglobulin superfamily (domain structure)Two different chainsVariable domains in contact with antigen (encoded by recombined DNA) Associated signal transduction molecules

Activation motif

Disulphide bond

Page 8: Antigen Receptors of Lymphocytes. Recognition: molecular patterns Recognition : molecular details (antigenic determinants) Innate immunity Aquired immunity

Signal trasduction

T cell receptor (TCR)

Antigen presenting cell

Signal trasduction

Membrane Ig

Antibody (Immunoglobulin)

Antigen Receptors of Lymphocytes - Differences

Recognizes: Free and membrane antigens Protein, polysaccharide, lipid, DNA, RNAConformational and linear epitopes

Recognizes :Antigens on the other cell membranePeptides only (αβ TCR)Linear epitopes

Page 9: Antigen Receptors of Lymphocytes. Recognition: molecular patterns Recognition : molecular details (antigenic determinants) Innate immunity Aquired immunity

Antigen Receptors of Lymphocytes - Differences

Recognizes: Free and membrane antigens Protein, polysaccharide, lipid, DNA, RNAConformational and linear epitopesConsists of:4 polypeptide chains (2H and 2L)

Recognizes: Antigens on the other cell membranePeptides only (αβ TCR)Linear epitopesConsists of:2 polypeptide chains (αβ or γδ)

Page 10: Antigen Receptors of Lymphocytes. Recognition: molecular patterns Recognition : molecular details (antigenic determinants) Innate immunity Aquired immunity

Antibody structure

Membrane of the B-cell

Page 11: Antigen Receptors of Lymphocytes. Recognition: molecular patterns Recognition : molecular details (antigenic determinants) Innate immunity Aquired immunity

"for their discoveries concerning the chemical structure of antibodies"

Gerald M. Edelman Rodney R. Porter

Nobel prize for physiology and medicine 1972

Page 12: Antigen Receptors of Lymphocytes. Recognition: molecular patterns Recognition : molecular details (antigenic determinants) Innate immunity Aquired immunity

Antibody structure

Heavy chain

Light chain Light chain

Heavy chain

Disulphide bonds

Antigen binding sites

Page 13: Antigen Receptors of Lymphocytes. Recognition: molecular patterns Recognition : molecular details (antigenic determinants) Innate immunity Aquired immunity

Antibody structure – papain digestion

Hinge region PapainFab fragments

Fc fragment

Interaction with other participants in the immune Response (cells, complement)

Antigen bindingAntibody structure

Page 14: Antigen Receptors of Lymphocytes. Recognition: molecular patterns Recognition : molecular details (antigenic determinants) Innate immunity Aquired immunity

Antibody structure – pepsin digestion

Pepsin

F(ab)2 fragment

Antigen binding

Page 15: Antigen Receptors of Lymphocytes. Recognition: molecular patterns Recognition : molecular details (antigenic determinants) Innate immunity Aquired immunity

MHC groove

Anchoring amino acids

Contact amino acid

Peptide

Polymorphic partsof MHC molecule

T-cell receptor

Page 16: Antigen Receptors of Lymphocytes. Recognition: molecular patterns Recognition : molecular details (antigenic determinants) Innate immunity Aquired immunity

TCR• Co-receptor molecules (CD4/CD8)

required

BCR• Recognition without

requirement for co-receptor molecules

Peptide

T-cell receptor (TCR)Immunoglobulin (Ig)