TY - JOUR
T1 - Determinants of immunodominance for CD4 T cells
AU - Kim, Ae Ryon
AU - Sadegh-Nasseri, Scheherazade
N1 - Funding Information:
Authors thank Dr. Isamu Z. Hartman who contributed to some of the work discussed here. This work was supported by grants from National Institute of Allergy and Infectious Diseases of Health (NIAID) of National Institute of Health, USA R01AI063764 and R21 AI101987 to SS-N. The following reagent was obtained through BEI Resources, NIAID, NIH: H5 Hemagglutinin (HA) Protein from Influenza Virus, A/Vietnam/1203/2004 (H5N1), Recombinant from Baculovirus, NR-10510.
Publisher Copyright:
© 2014 Elsevier Ltd.
PY - 2015/6/1
Y1 - 2015/6/1
N2 - The term immunodominance was originally defined as a restricted T cell response to a short peptide sequence derived from a given protein [1]. The question of what determines immunodominance has been a longstanding battle for the past two decades. Hundreds of papers have been written on different aspects of epitope selection during antigen processing documenting the complexity of the process. Antigen processing machinery involves several accessory molecules and chaperons coevolved with proteins of Major Histocompatibility Complex (MHC) molecules that each plays its part in epitope selection. These molecules are targeted to specialized vesicular compartments that also accommodate antigen processing enzymes called cathepsins. Within the antigen processing compartments, highly regulated pH gradient and reducing conditions and enzymes necessary for denaturation of the antigens are available and function to optimize processing of antigen and selection of the fittest for transport to the cell membrane and presentation to T cells. Despite the complexity, a cell free reductionist antigen processing system was recently reported that included only few purified proteins, but was shown to process and select physiologically relevant epitopes from full length protein antigens [2••]. Due to its minimalist nature the system has been quite helpful in dissecting the factors that contribute to epitope selection during antigen processing. In this review, we would summarize and highlight models that may explain how the dominant epitope may be selected for presentation to CD4+ helper T cells.
AB - The term immunodominance was originally defined as a restricted T cell response to a short peptide sequence derived from a given protein [1]. The question of what determines immunodominance has been a longstanding battle for the past two decades. Hundreds of papers have been written on different aspects of epitope selection during antigen processing documenting the complexity of the process. Antigen processing machinery involves several accessory molecules and chaperons coevolved with proteins of Major Histocompatibility Complex (MHC) molecules that each plays its part in epitope selection. These molecules are targeted to specialized vesicular compartments that also accommodate antigen processing enzymes called cathepsins. Within the antigen processing compartments, highly regulated pH gradient and reducing conditions and enzymes necessary for denaturation of the antigens are available and function to optimize processing of antigen and selection of the fittest for transport to the cell membrane and presentation to T cells. Despite the complexity, a cell free reductionist antigen processing system was recently reported that included only few purified proteins, but was shown to process and select physiologically relevant epitopes from full length protein antigens [2••]. Due to its minimalist nature the system has been quite helpful in dissecting the factors that contribute to epitope selection during antigen processing. In this review, we would summarize and highlight models that may explain how the dominant epitope may be selected for presentation to CD4+ helper T cells.
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U2 - 10.1016/j.coi.2014.12.005
DO - 10.1016/j.coi.2014.12.005
M3 - Review article
C2 - 25576665
AN - SCOPUS:84920683669
SN - 0952-7915
VL - 34
SP - 9
EP - 15
JO - Current Opinion in Immunology
JF - Current Opinion in Immunology
ER -