Human CD8+ T cells recognize epitopes of the 28-kDa hemolysin and the 38-kDa antigen of Mycobacterium tuberculosis

Homayoun Shams^*^,^,1, Peter F. Barnes^*^,^,, Stephen E. Weis, Peter Klucar^*^, and Benjamin Wizel^*^,

^* Center for Pulmonary and Infectious Disease Control, Departments of
Microbiology and Immunology and
Medicine, University of Texas Health Center, Tyler; and
Department of Internal Medicine, University of North Texas Health Sciences Center, Fort Worth

¹Correspondence: CPIDC, UT Health Center, 11937 U.S. Hwy. 271, Tyler, TX 75708-3154. E-mail: amir.shams{at}uthct.edu

Mycobacterium tuberculosis antigens that are recognized by humanCD8+ T cells are potentially important vaccine target molecules.We used a motif-based strategy to screen selected proteins ofM. tuberculosis for peptides predicted to bind to human leukocyteantigen (HLA)-A*0201. We identified two 10 amino acid peptidesthat elicited cytolytic T lymphocyte activity and interferon- ${gamma}$ production by CD8+ T cells from HLA-A*0201+ healthy tuberculinreactors. These peptides were derived from the 38-kDa antigenand the 28-kDa hemolysin, the latter being a novel target forCD8+ T cells. We speculate that hemolysins may alter the phagosomalmembrane surrounding intracellular M. tuberculosis, allowingthemselves and other antigens to gain access to the major histocompatibilitycomplex class I processing pathway.

Key Words: cytolytic T lymphocyte • HLA-A*0201 • Bacillus Calmette-Guerin • Interferon gamma