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Infection and Immunity, March 2006, p. 1621-1630, Vol. 74, No. 3
0019-9567/06/$08.00+0     doi:10.1128/IAI.74.3.1621-1630.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Role of Phagosomes and Major Histocompatibility Complex Class II (MHC-II) Compartment in MHC-II Antigen Processing of Mycobacterium tuberculosis in Human Macrophages

Martha Torres,^1,5, Lakshmi Ramachandra,^2,4,* Roxana E. Rojas,¹ Karen Bobadilla,⁵ Jeremy Thomas,¹ David H. Canaday,¹ Clifford V. Harding,^3, and W. Henry Boom^1,

Division of Infectious Disease,¹ Department of Pediatrics,² Department of Pathology, Case Western Reserve University, Cleveland, Ohio,³ Rainbow Babies and Children's Hospital, Cleveland, Ohio,⁴ Departamento de Microbiologia, Instituto Nacional de Enfermedades Respiratorias, Mexico City, Mexico⁵

Received 7 September 2005/ Returned for modification 13 October 2005/ Accepted 7 December 2005

Mycobacterium tuberculosis resides in phagosomes inside macrophages. In this study, we analyzed the kinetics and location of M. tuberculosis peptide-major histocompatibility complex class II (MHC-II) complexes in M. tuberculosis-infected human macrophages. M. tuberculosis peptide-MHC-II complexes were detected with polyclonal autologous M. tuberculosis-specific CD4⁺ T cells or F9A6 T hybridoma cells specific for M. tuberculosis antigen (Ag) 85B (96-111). Macrophages processed heat-killed M. tuberculosis more rapidly and efficiently than live M. tuberculosis. To determine where M. tuberculosis peptide-MHC-II complexes were formed intracellularly, macrophages incubated with heat-killed M. tuberculosis were homogenized, and subcellular compartments were separated on Percoll density gradients analyzed with T cells. In THP-1 cells, M. tuberculosis Ag 85B (96- 111)-DR1 complexes appeared initially in phagosomes, followed by MHC class II compartment (MIIC) and the plasma membrane fractions. In monocyte-derived macrophages, M. tuberculosis peptide-MHC-II complexes appeared only in MIIC fractions and subsequently on the plasma membrane. Although phagosomes from both cell types acquired lysosome-associated membrane protein 1 (LAMP-1) and MHC-II, THP-1 phagosomes that support formation of M. tuberculosis peptide-MHC-II complexes had increased levels of both LAMP-1 and MHC-II. Thus, M. tuberculosis phagosomes with high levels of MHC-II and LAMP-1 and MIIC both have the potential to form peptide-MHC-II complexes from M. tuberculosis antigens in human macrophages.

Editor: W. A. Petri, Jr.

These two authors (Martha Torres and Lakshmi Ramachandra) contributed equally to this work.

These two authors share senior authorship.

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