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
[1], [3].
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].
References:
- Hsing LC, Rudensky AY
The lysosomal cysteine proteases in MHC class II antigen presentation.
Immunological reviews 2005 Oct;207:229-41
- 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
- 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
- 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
