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antigen. T Cell Antigen Specificity - a:b. Antigen determinant = epitope - Part of antigen that binds antigen receptor T cells with a:b TCR are specific for denatured or fragmented (peptides) forms of protein antigens which are linear determinants
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T Cell Antigen Specificity - a:b • Antigen determinant = epitope - Part of antigen that binds antigen receptor • T cells with a:b TCR are specific for denatured or fragmented (peptides) forms of protein antigens which are linear determinants • Antibodies specific for TCR or MHC inhibit T cell responses, but those specific for intact antigens rarely inhibit • CD4+ T cells usually recognize exogenous antigens, while CD8+ T cells usually recognize endogenous antigens • This dichotomy is NOT mutually exclusive
Protein antigens cleaved by cathepsins
Invariant Chain & MHC Class II Associate in ER Blocks cleft Sorting signal
cathepsins MIIC
Second peptide exchange
Treatment of presenting cells with brefeldin A may or may not interfere with antigen processing
Mechanism of Antigen Processing • Lysosomotropic agents usually do not inhibit killing of target cells • Viral proteins are synthesized by target cells Target cells incubated with UV irradiated virus are not killed Target cells incubated with intact viral proteins are not killed • Brefeldin A blocks target cell killing
Long peptides trimmed
Important Concepts • Antigen processing for both pathways is an integral part of synthesis and assembly of MHC class I & class II molecules • The two antigen processing pathways are not completely separated • Intracellular transport inside antigen-presenting cells allows antigens to access both pathways
molecules Autophagy - macro or micro
Retrograde Cross Presentation
Involvement of Retrograde Translocation ER