Francisco Borrego, M.D., Ph.D.
Staff Scientist
Dr. Borrego received his M.D. and his Ph.D. in immunology at the University of Cordoba in Spain. Under the supervision of Professor Jose Pena and Professor Rafael Solana, he investigated the cellular and molecular events leading to the activation of human natural killer (NK) cells. In 1995, he moved to the Laboratory of Molecular Structure at NIAID, NIH, to work with Dr. John E. Coligan in the characterization of NK-cell receptors. In 1998, he joined the Laboratory of Allergic Diseases, and in 2000, he became a staff scientist in the Receptor Cell Biology Section.
Description of Research Program
The immune system must be tightly regulated to avoid poor responses on one side and autoimmunity on the other. The balance between activating and inhibitory signals determines the outcome of the immune response. In the past, we have studied activating and inhibitory receptors in the NK complex, the CD94/NKG2 family of receptors, and NKG2D. These receptors are primarily expressed on NK and CD8+ T cells. We have shown that CD94/NKG2A inhibitory receptors, after interaction with HLA-E on target cells, form an inhibitory synapse that is characterized by the exclusion of lipid rafts and decreased mobility of the receptor. We also have shown that the activating receptor, NKG2D, can serve as a costimulatory receptor for human naïve CD8+ T cells, providing an alternative mechanism for potentiating and channeling immune responses.
Recently, two inhibitory receptors, CD300a (IRp60) and CD305 (LAIR-1), have been described. The pattern of expression of these receptors differs from the CD94/NKG2 and NKG2D receptors. CD300a and CD305 are expressed by almost all leukocyte subsets. The ligands of these inhibitory receptors are not known, and we are employing biochemical and functional approaches to identify them. In addition, the role of these receptors in leukocyte populations is being studied, and so far, we have shown that they inhibit T-cell responses. We have also generated LAIR-1 knockout mice and are starting to study the role of this receptor in vivo. We think that these receptors will have an important role in regulating immune responses. A polymorphism in the CD300a gene has been associated with development of psoriasis, indicating the involvement of this receptor in regulating autoimmune responses. As with LAIR-1, to understand the role of CD300a in vivo, we are generating the LMIR1 knockout mouse. LMIR1 is the murine homolog of CD330a.
Major Areas of Research
- Characterization of the ligands for CD300a and CD305
- Role of CD300a and CD305 in the function of leukocyte subsets, including lymphocytes, neutrophils, and dendritic cells
- Role of CD300a and CD305 in controlling immune responses in vivo
Memberships
- American Association of Immunologists
- Society for Natural Immunity
Editorial Boards
Selected Recent Publications
To view a complete listing, visit PubMed.
Lieto LD, Maasho K, West D, Borrego F, Coligan JE. The human CD94 gene encodes multiple, expressible transcripts including a new partner of NKG2A/B. Genes Immun. 2006. 7: 36-43.
Maasho K, Masilamani M, Valas R, Basu S, Coligan JE, Borrego F. 2005. The inhibitory leukocyte-associated Ig-like receptor-1 (LAIR-1) is expressed at high levels by human naïve T cells and inhibits TCR mediated activation. Mol Immunol. 2005. 42: 1521-1530.
Maasho K, Opoku-Anane J, Marusina AI, Coligan JE, Borrego F. NKG2D is a costimulatory receptor for human naïve CD8+ T cells. J Immunol. 2005. 174: 4480-4484.
Borrego F, Masilamani M, Kabat J, Sanni TB, Coligan JE. The cell biology of the human natural killer cell CD94/NKG2A inhibitory receptor. Mol Immunol. 2005. 42: 485-488.
Sanni TB, Masilamani M, Kabat J, Coligan JE, Borrego F. Exclusion of lipid rafts and decreased mobility of CD94/NKG2A receptors at the inhibitory NK cell synapses. Mol Biol Cell. 2004. 15: 3210-3223.
Lieto LD, Borrego F, You CH, Coligan JE. Human CD94 gene expression: dual promoters differing in responsiveness to IL-2 or IL-15. J Immunol. 2003. 171: 5277-5286.
Borrego F, Kabat J, Sanni T, Coligan JE. CD94/NKG2A recycling and transmission of the inhibitory signal are two independent processes. J Immunol. 2002. 169: 6102-6111.
Kabat J, Borrego F, Brooks AG, Coligan JE. Role that each NKG2A immunoreceptor tyrosine-based inhibitory motif plays in generating the CD94/NKG2A inhibitory signal. J Immunol. 2002. 169: 1948-1958.
Borrego F, Kabat J, Kim D-K, Lieto L, Maasho K, Pena J, Solana R, Coligan JE. Structure and function of major histocompatibility complex (MHC) class I specific receptors expressed on human natural killer (NK) cells. Mol Immunol. 2002. 38: 637-660.
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