M4L2 Antigen presentation and recognition

Antigens on B cells = immunoglobulins

Antigens on T cells = TCRs

The adaptive immune system views the world of antigens through the lens of MHC molecules and the cargo they present

MHCs are highly poolymorphic, presenting unique sets of peptides

MHC restriction - any given TCR is specific for a particular peptide bond to a particular MHC molecule

All MHCs have similar 3D structure but different subunit compoisition

• MHC I - heterodimer of membrane spanning alpha chain bound non covalents to B2 microglobulin 

  • Alpha chain folds into a1, a2, a3

  • Peptide binding cleft or groove

  • Major differences between MHC alleles are in the cleft,  influencing peptide binding and specificity of the dial antidegn presented to T cells

  • On all nucleated cells

• MHC II - 2 TM alpha and beyta glycoprotein chains

  • Each chain has two domains which forms compact structure

  • Two domains form the beptide binding cleft and not joined by covalent bond

  • Ends of peptide cleft are more open  than MHC I

  • Sites of polymorphism - peptide binding groove

  • Expressed on APCs

  • Presentation of exogenous antigens taken up by APCs to CD4+ Th cells.

    IFN-γ increases the expression of MHC Class II molecules

Binding of peptide on MHC is an indicator of infection or abnormality

Immunopeptidomics - determination by mass spec of peptides bound to MHCs

MHC I present peptides frome endogenous proteins and MHC II mostly samples extracellular world

Cells in MHC II restricted presentation acquire antigens thrpough phagocytosis and endocytosis

MHC I molecules sample thr proteome of MHC I+ cells