Pathway maps

Immune response_Antigen presentation by MHC class II
Immune response_Antigen presentation by MHC class II

Object List (links open in MetaCore):

CD74, IP-30, HLADRA, HLA-DM, MHC class II, TCR alpha/beta, Cathepsin L, CD3, CD4, Antigen, Legumain, Cathepsin S, MHC class II


Antigen presentation by MHC class II

Antigen processing and presentation is the process by which antigen-presenting cells express antigen on cell surface in a form recognizable by lymphocytes. Antigen processing consists of protein fragmentation (proteolysis), association of fragments with MHC (major histocompatibility complex) and expression of peptide-MHC complex at cell surface where they can be recognized by T cell receptor ( TCR ).

Expression of MHC genes is constitutively activated during development in professional antigen-presenting cells, such as B cells, dendritic cells, and macrophages.

There are two classes of MHC molecules, MHC class I and MHC class II. MHC class II proteins specialize in presentation of exogenous antigens to TCR of CD4+ T-cells.

Exogenous proteins are endocytosed and degraded by acidic proteases ( Legumain, Cathepsin L and Cathepsin S ) resident within endosomes and lysosomes [1]. Gamma-interferon-inducible lysosomal thiol reductase IP-30 facilitates unfolding of endocytosed antigens in MHC class II -containing compartments by enzymatic cleavage of disulfide bonds [2].

MHC class II molecules are assembled in the endoplasmic reticulum by the chaperone CD74, which directs these complexes to the endosomal compartments. Processing of CD74 includes its initial cleavage by Legumain, followed by late stage cleavage by Cathepsin S and Cathepsin L [3], [1].

HLA-DM, a vesicle membrane protein, mediates CD74 removal (its last small fragment) from MHC class II polypeptides, and then MHC class II molecules are capable to bind antigens. MHC class II - Antigen complex is then transported to cell surface for presentation to CD4+ T-cells [4].


  1. Hsing LC, Rudensky AY
    The lysosomal cysteine proteases in MHC class II antigen presentation. Immunological reviews 2005 Oct;207:229-41
  2. Phan UT, Lackman RL, Cresswell P
    Role of the C-terminal propeptide in the activity and maturation of gamma -interferon-inducible lysosomal thiol reductase (GILT). Proceedings of the National Academy of Sciences of the United States of America 2002 Sep 17;99(19):12298-303
  3. Watts C, Matthews SP, Mazzeo D, Manoury B, Moss CX
    Asparaginyl endopeptidase: case history of a class II MHC compartment protease. Immunological reviews 2005 Oct;207:218-28
  4. Busch R, Rinderknecht CH, Roh S, Lee AW, Harding JJ, Burster T, Hornell TM, Mellins ED
    Achieving stability through editing and chaperoning: regulation of MHC class II peptide binding and expression. Immunological reviews 2005 Oct;207:242-60