Dr. Rajalingam Raja's research focus is on the natural killer (NK) cells and cytotoxic T-lymphocytes (CTL), which are the integral components of cell-mediated cytotoxicity (CMI) that govern early response to infection. The action of both NK cells and CTL is controlled by the interaction of their specific receptors with class I human leukocyte antigens (HLA) expressed on the surface of target cells. The class I receptor-repertoire of CTL comprises of T-cell receptors (TCR) and accessory molecules, and the TCR diversity is generated through somatic gene rearrangements. Contrarily, the NK cell receptor-repertoire is constituted by structurally and functionally divergent products of two polygenic families: killer cell Ig-like receptors (KIR) of Ig-super gene family, and dimmers of CD94 and NKG2 proteins with lectin-like domains. Unlike TCR-repertoire, the diversity of NK cell receptor-repertoire is determined by a combined genetic, transcriptional and translational factors.
Haplotypic variation in the number and type of KIR genes and allelic polymorphism of each KIR genes individualize the human genome. Further, alternative mRNA splicing and clonal expression pattern of each KIR gene diversify the NK cells within an individual. The NK cell receptors have distinct HLA specificity. Since both KIR and HLA systems are polymorphic and located on different chromosomes they segregate independently into germ cells. This produces a population diversity in the number and type of KIR:HLA pairs inherited, which determine the strength of CMI against the invading pathogens. His current research studies the diversity and polymorphism of NK cell receptor repertoire, HLA class I ligands and their combinations in human health and disease.
Selected Cancer-Related Publications:
Ashouri E, Farjadian S, Reed EF, Ghaderi A, Rajalingam R. KIR gene content diversity in four Iranian populations. Immunogenetics. 2009 Jul;61(7):483-92. Epub 2009 Jun 12.
Bonagura VR, Du Z, Ashouri E, Luo L, Hatam LJ, DeVoti JA, Rosenthal DW, Steinberg BM, Abramson AL, Gjertson DW, Reed EF, Rajalingam R. Activating killer cell immunoglobulin-like receptors 3DS1 and 2DS1 protect against developing the severe form of recurrent respiratory papillomatosis. Hum Immunol. 2010 Feb;71(2):212-9. Epub 2009 Oct 25.
Rajalingam R. Variable interactions of recipient killer cell immunoglobulin-like receptors with self and allogenic human leukocyte antigen class I ligands may influence the outcome of solid organ transplants. Curr Opin Organ Transplant. 2008 Aug;13(4):430-7.
Rajalingam R, Du Z, Meenagh A, Luo L, Kavitha VJ, Pavithra-Arulvani R, Vidhyalakshmi A, Sharma SK, Balazs I, Reed EF, Pitchappan RM, Middleton D. Distinct diversity of KIR genes in three southern Indian populations: comparison with world populations revealed a link between KIR gene content and pre-historic human migrations. Immunogenetics. 2008 May;60(5):207-17. Epub 2008 Mar 28.
Du Z, Sharma SK, Spellman S, Reed EF, Rajalingam R. KIR2DL5 alleles mark certain combination of activating KIR genes. Genes Immun. 2008 Jul;9(5):470-80. Epub 2008 May 29.