Thiol oxidation and reduction in MHC-restricted antigen processing and presentation

Major histocompatibility complex (MHC) class I molecules are assembled in t he endoplasmic reticulum (ER) as a trimer of the class I heavy chain, beta( 2) microglobulin (beta(2)m), and a short peptide. Assembly occurs in a comp lex with additional noncovalently associated proteins, which include the th iol oxidoreductase, ERp57. This molecule facilitates the formation of the c orrect disulfide bonds in glycoproteins as they fold in the ER and may play a key role in assembling a stable MHC class I-peptide complex. In the endo cytic pathway, reduction of protein disulfide bonds is important for the ge neration of MHC class II-peptide complexes. This process is catalyzed by a gamma-interferon-inducible thiol reductase (GILT), The possible requirement for catalysis of disulfide bond formation in MHC class I-restricted antige n processing and the known requirement for disulfide bond reduction in MHC class II-restricted antigen processing present interesting examples of the adaptation of cellular "housekeeping" functions to facilitate immune respon ses.