Characterization of a Mycobacterium tuberculosis peptide that is recognized by human CD4+ and CD8+ T cells in the context of multiple HLA alleles.
The secreted Mycobacterium tuberculosis 10-kDa culture filtrate protein (CFP)10 is a potent T cell Ag that is recognized by a high percentage of persons infected with M. tuberculosis. We determined the molecular basis for this widespread recognition by identifying and characterizing a 15-mer peptide, CFP10(71-85), that elicited IFN-gamma production and CTL activity by both CD4(+) and CD8(+) T cells from persons expressing multiple MHC class II and class I molecules, respectively. CFP10(71-85) contained at least two epitopes, one of 10 aa (peptide T1) and another of 9 aa (peptide T6). T1 was recognized by CD4(+) cells in the context of DRB1*04, DR5*0101, and DQB1*03, and by CD8(+) cells of A2(+) donors. T6 elicited responses by CD4(+) cells in the context of DRB1*04 and DQB1*03, and by CD8(+) cells of B35(+) donors. Deleting a single amino acid from the amino or carboxy terminus of either peptide markedly reduced IFN-gamma production, suggesting that they are minimal epitopes for both CD4(+) and CD8(+) cells. As far as we are aware, these are the shortest microbial peptides that have been found to elicit responses by both T cell subpopulations. The capacity of CFP10(71-85) to stimulate IFN-gamma production and CTL activity by CD4(+) and CD8(+) cells from persons expressing a spectrum of MHC molecules suggests that this peptide is an excellent candidate for inclusion in a subunit antituberculosis vaccine.
Shams
Homayoun
H
Center for Pulmonary and Infectious Disease Control, and Department of Microbiology, University of Texas Health Center, Tyler, TX 75708, USA. amir.shams@uthct.edu
Klucar
Peter
P
Weis
Steven E
SE
Lalvani
Ajit
A
Moonan
Patrick K
PK
Safi
Hassan
H
Wizel
Benjamin
B
Ewer
Katie
K
Nepom
Gerald T
GT
Lewinsohn
David M
DM
Andersen
Peter
P
Barnes
Peter F
PF
D000483:Alleles; D019943:Amino Acid Substitution; D000942:Antigens, Bacterial / Q000276:immunology*; D001426:Bacterial Proteins / Q000737:chemistry / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D003602:Cytotoxicity, Immunologic; D000939:Epitopes / Q000737:chemistry / Q000276:immunology; D006680:HLA Antigens / Q000276:immunology*; D006683:HLA-DQ Antigens / Q000276:immunology; D059866:HLA-DQ beta-Chains; D006684:HLA-DR Antigens / Q000276:immunology; D059811:HLA-DRB1 Chains; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology*; D017384:Sequence Deletion; D037182:T-Cell Antigen Receptor Specificity; D032581:Tuberculosis Vaccines
D000942:Antigens, Bacterial; D001426:Bacterial Proteins; C489634:CFP-10 protein (71-85), Mycobacterium tuberculosis; C117940:CFP-10 protein, Mycobacterium tuberculosis; D000939:Epitopes; D006680:HLA Antigens; D006683:HLA-DQ Antigens; D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D010446:Peptide Fragments; D032581:Tuberculosis Vaccines; D007371:Interferon-gamma