Edmond J. Yunis
Dana-Farber Cancer Institute
Dana Bldg., Rm.740
44 Binney Street
Boston, MA 2115
The main research focus of our laboratory is to establish the cellular, molecular, and genetic basis for the immunopathogenesis of susceptibility to develop active disease after Mycobaterium tuberculosis (Mtb) infection and AIDS after HIV-1 infection, susceptibility to autoimmune diseases and allotransplantation. Found evidence that the increasing incidence of autoimmune diseases are due to population admixture (1). We described different sizes of DNA blocks in the MHC and studied the region of Class 1 (2). In the area of HIV-1 infection and progression to AIDS, we have established an association homozygosity of HLA-B alleles of the HLA-Bw4 public specificity and HLA-B44 alleles with control of HIV viremia and protection from AIDS exists. We are currently in search for the mechanisms of protection. We know that the HLA-B locus is located close to the MICA and MICB loci (encoding the ligands of NKG2D receptors) and that some HLA-B alleles can be inherited in linkage disequilibrium with alleles of these genes. Protection from AIDS may also have something to do with the fact that almost all HLA-B alleles of the Bw4 specificity and some of the Bw6 specificity encode leader peptides that when digested in the proteasome generate nona-peptides that interfere with the folding and expression of HLA-E molecules. This may hamper the delivery of inhibitory signals through the HLA-E/CD94-NKG2A pathway to NK and some CD8+ T cells in almost all individuals carrying Bw4 alleles and some carrying Bw6 alleles, resulting in killing of HIV infected cells and protection from developing AIDS (3). Described strategies for typing for allotransplantation (4). The tuberculin skin test that detects T cell responses of delayed type hypersensitivity type IV. Since it produces false negative reactions in active tuberculosis or in high-risk persons exposed to tuberculosis, we studied antibody profiles to explain the anergy of such responses in high-risk individuals without active infection.. Humoral immunity against tuberculin, regardless of the result of the tuberculin skin test is important for protection from active tuberculosis and that the presence of high antibody titers is a more reliable indicator of infection latency suggesting that latency can be based on the levels of antibodies together with in vitro proliferation of peripheral blood mononuclear cells in the presence of the purified protein derivative. Importantly, anti-tuberculin IgG antibody levels could prevent reactivation of disease in high-risk individuals with high antibody titers. Such anti-tuberculin IgG antibodies were also found associated with blocking and/or stimulation of in vitro cultures of PBMC with tuberculin; immune responses to Mycobacterium tuberculosis can generate a broad spectrum of reactions either toward Th1 responses favoring stimulation by cytokines or by antibodies and those toward diminished responses by Th2 cytokines or blocking by antibodies; possibly involving mechanisms of antibody dependent protection from Mtb by different subclasses of IgG (5).
1. Z Awdeh ZL, Yunis EJ, Audeh M, Fici D, Pugliese P, Larsen CE, Alper CA. A genetic explanation for the rising incidence of a polygenic disease, Journal of autoimmunity. J of Autoimmun. 2006; 27(3): 174-81.
2. Romero V, Larsen CE, Duke-Cohan JS, Fox EA, Romero T, Clavijo OP, Fici DA, Husain Z, Almeciga I, Alford DR, Awdeh ZL, Zuñiga J, El-Dahdah L, Alper CA, Yunis EJ. Genetic fixity in the human major histocompatibility complex and block size diversity in the class I region including HLA-E. BMC Genetics. 2007; 8:14-.
3. Yunis EJ, Romero V, Diaz-Giffero F, Zuñiga J, Koka P. Natural Killer Cell Receptor NKG2A/HLA-E Interaction Dependent Differential Thymopoiesis of Hematopoietic Progenitor Cells Influences the Outcome of HIV Infection. J Stem Cells. 2007; 2:237-248.
4. Williams TM, Winden T, Setterholm M, Vierra-Green CA, Spellman S, Flesch S, Awdeh Z, Baxter-Lowe LA, Begovich AB, Fernandez-Viña M, Hegland J, Hurley CK, Johnson D, Noreen H, Salazar M, Schmeckpeper B, Yunis EJ. Strategies and technical challenges in allele level Class II typing in 2578 bone marrow transplantation donor-recipient pairs. Hum Immunol. 2008; 69(4-5); 227-34.
5. Liliana Encinales, Joaquin Zuñiga, Julio Granados-Montiel, Maria Yunis, Julio Granados, Ingrid Almeciga, Olga Clavijo, Carlos Awad, Vilma Collazos, María Inés Vargas-Rojas, José Luis Banales-Mendez. Lilia Vazquez-Castañeda, Joel N. Sterna, Viviana Romero, Masha Frindkis-Hareli, Daniel Terreros, Marcelo Fernandez-Viña, Edmond J. Yunis. Humoral immunity in tuberculin skin test anergy and its role in high-risk persons exposed to active tuberculosis. Molecular Immunology 2010; 47:1066-1073.
Last Update: 1/6/2014