First study that used a direct biochemical assay rather than a T cell 'readout' to detect capture of processed antigen by class II MHC molecules. This study show that antigen presentation to CD4+ T cells relies on newly synthesized MHC class II molecules.
Processed antigen binds to newly synthesized MHC class II molecules in antigen-specific B lymphocytes
Davidson, H.W., Reid, P.A., Lanzavecchia, A. & Watts, C.
This study shows presentation of peptides from a protein that was experimentally injected into the cytosol of cells. Thus, actual synthesis of peptide by the presenting cell is not necessary for MHC class I presentation. This observation helped identify the cytosol as a location where antigen processing was likely to occur.
Introduction of soluble protein into the class I pathway of antigen processing and presentation
This study demonstrates that fragments of proteins expressed in the cytosol are presented on MHC class I molecules. This finding went against the prevailing view that CTLs recognize intact antigens on the plasma membrane.
Cytotoxic T lymphocytes recognize influenza haemagglutinin that lacks a signal sequence
Townsend, A.R., Bastin, J., Gould, K. & Brownlee, G.G.
This paper changed the dogma of MHC class I antigen presentation by showing that CD8+ T cells recognize degradation products (short peptide fragments) in association with MHC class I molecules. In the early 1980s, when the basic features of the MHC class II processing pathway were being defined, it was believed that MHC class I—restricted T cells recognized intact endogenously synthesized proteins expressed in the plasma membrane in association with MHC class I molecules.
The epitopes of influenza nucleoprotein recognized by cytotoxic T lymphocytes can be defined with short synthetic peptides
This paper defined a key difference in the MHC class I and MHC class II processing pathways, demonstrating that viral antigens must be endogenously synthesized in target cells for recognition by CD8+ T cells, whereas endogenous synthesis was not required for presentation of viral antigen to MHC class II—restricted CD4+ T cells.
Differences in antigen presentation to MHC class I- and class II-restricted influenza virus-specific cytolytic T lymphocyte clones
Until the mid-1980s, the requirement for physical linkage of T and B cell antigenic determinants to generate T cell—dependent antibody responses (the carrier effect) was explained by an 'antigen-bridge' model, in which simultaneous recognition of different determinants on the same antigen molecule brought T and B cells into physical contact. This model was inconsistent with emerging evidence that helper T cells recognize processed peptides, whereas B cells recognize conformational determinants. Two classic papers demonstrated that the requirement for physical linkage could be explained by the fact that antigen specific B cells are much more efficient at uptake and processing antigens internalized through the B cell antigen receptor.
Antigen presentation by hapten-specific B lymphocytes. II. Specificity and properties of antigen-presenting B lymphocytes, and function of immunoglobulin receptors
Ziegler and Unanue demonstrated that the kinetics of antigen catabolism in macrophages correlates with antigen processing and that inhibitors of antigen uptake or catabolism inhibits antigen recognition by T cells. This work built on previous studies that lead to the general concept that T cells recognize both antigen and MHC molecules on the surface of macrophages or other accessory cells and that T cells recognize sequential rather than conformational determinants in protein antigens.
Decrease in macrophage antigen catabolism caused by ammonia and chloroquine is associated with inhibition of antigen presentation to T cells
This study demonstrated that there was a period of time after antigen-presenting cells were exposed to antigen during which (but not after) fixation blocked their ability to present antigen on MHC class II molecules. This was the first demonstration that an antigen processing step was necessary to antigen presentation.
Identification of a macrophage antigen-processing event required for I-region-restricted antigen presentation to T lymphocytes
