1 Instructor, 2 Post-Doctoral fellows, 4 Research Technicians

Our laboratory is focusing on the study of cellular immune responses to viral infections in the immune compromised host.  While the main focus is on HIV, we have also performed studies on the characterization of Kaposi’s Sarcoma Herpesvirus (KSHV)- and EBV-specific T cell responses in different clinical settings.  These include individuals with reduced immune competence due to advanced HIV infection as well as subjects undergoing solid organ transplantation.

The studies on HIV specific immunity address how the host cellular immune response and viral sequence variation are interlinked and what implications the ongoing global viral diversification has on HIV vaccine design. Also, the role of host genetics, especially HLA class I polymorphisms are being investigated by studying cellular immune responses in individuals of different ethnic backgrounds, including subjects in the US, South Africa, Barbados and Peru. These studies provide insight on T cell cross-reactivity, promiscuous epitope HLA restriction, and the role of T cell receptor diversity in the recognition of epitope escape variants.

The studies on herpes-virus specific immunity address the host control of these viruses in healthy virus carriers and in the settings of reduced immune competence.  In particular, subjects developing active Kaposi’s Sarcoma or proliferative disorders post-transplantation or in the course of advanced HIV infection are being studied.  An extension of this work, performed in the research laboratory in Lima, Peru investigates how acute HIV may impact on the pre-existing immune response to these viral co-pathogens and predispose virus-carriers to the development of virus-driven malignant disorders.

Important Past Accomplishments:

1. Since 1995, the members of the Brander lab have provided annual updates to the HIV CTL epitope list at the Los Alamos National Laboratory HIV Immunology database.
2. Identification of differences in the epitope-specific response rates during acute or chronic HIV infection in the context of HLA-A2.
3. Demonstration of the effectiveness of sub-dominant T cell responses in the control of HIV.
4. Identification of  novel HLA class I alleles associated with slow or fast HIV disease progression, depending on the population allele frequency.
5. Definition of factors determining immunodominance patterns in acute and chronic EBV and HIV infection.
6. First identification of KSHV derived HLA class I restricted CTL epitope.
7. Identification of CTL-expressed CD103 as a novel ligand for E-Cadehrin in the tonsil.

Publications of Interest:

Goulder P, Altfeld M, Rosenberg E, Nguyen T, Tang Y, Eldridge R, Addo M, He S, Mukerjee J, Phillips M, Ogg G, Kalams S, Sekaly R, Walker B, Brander C.  Substantial differences in specificity of HIV specific cytotoxic T cells in acute and chronic HIV infection.  J Exp Med 2001;193:181-194.

Brander C, O’Connor P, Suscovich T, Jones N, Lee Y, Kedes D, Ganem D, Martin J, Osmond D, Southwood S, Sette, A, Walker BD, Scadden DT.  Definition of an optimal cytotoxic T lymphocytes (CTL) epitope in the latently expressed Kaposi’s sarcoma associated herpes virus (KSHV) kaposin protein. J Inf Dis 2001;184:119-126.

Suscovich TJ, Paulose-Murphy M, Harlow JD, Chen Y, Thomas SY, Mellott TJ, Walker BD, Scadden DT, Zeichner S, Brander C. Defective immune function of Primary Effusion Lymphoma cells is associated with distinct KSHV gene expression profiles. Leukemia and Lymphoma, 2004, 45:1223-38.

SenGupta D, Norris PJ, Suscovich TJ, Hassan-Zahraee M, Moffett HF, Trocha, A, Draenert R, Goulder PJ, Binder RJ, Levey DL, Walker BD, Srivastava PK, Brander C. Heat shock protein-medicated cross-presentation of exogenous HIV antigen on HLA class I and class II. J Immunol. 2004; 173(3): 1987-93

Woodberry T, Henry L, August M, Wang F, Scadden DT, Brander C. aEb7 (CD103) identifies tonsil-resident, EBV-specific effector-memory CTL absent from the peripheral blood. J. Immunol. 2005; 175:4355-62.

Frahm N, Kiepiela P, Adams S, Linde CH,  Hewitt HS, Sango K, Feeney ME, Addo MM, Lichterfeld M, Lahaie MP, Pae E, Wurcel AG, Roach T, St John MA, Altfeld M, Marincola FM, Moore C, Mallal S, Carrington M, Allen TM, Mullins J, Heckerman D, Korber BT, Goulder PJR, Walker BD, Brander C.  Control of human immunodeficiency virus replication by cytotoxic T lymphocytes targeting subdominant epitopes. Nature Immunol. 2006, 7:173-8.

Bihl F, Frahm N, Di Giammarino L, Sidney J, John M, Yusim K, Woodberry T, Sango K, Hewitt HS, Henry L, Linde CH, Chisholm III JV, Zaman TM, Pae E, Mallal S, Walker BD, Sette A, Korber BT, Heckerman D, Brander C. Impact of HLA-B alleles, epitope binding affinity, functional avidity, and viral co-infection on the immunodominance of virus specific CTL responses. J. Immunology, 2006;176(7):4094-101

Additional Information
For additional information please contact:

Christian Brander, Ph.D.
Associate Professor of Medicine
Partners AIDS Research Center
Massachusetts General Hospital
Harvard Medical School
Bldg. 149, 13th Street, Rm 5239
Charlestown, MA 02129
Phone 617 724-5789
Fax 617 726-5411
cbrander@partners.org