Lloyd J. Old discovered the first linkage between the major histocompatibility complex (MHC) and disease—mouse leukemia—opening the way for the recognition of the importance of the MHC in the immune response.
The major histocompatibility complex (MHC) is a large locus on vertebrate DNA containing a set of closely linked polymorphic genes that code for cell surface proteins essential for the adaptive immune system. These cell surface proteins are called MHC molecules.
This locus got its name because it was discovered via the study of transplanted tissue compatibility. Later studies revealed that tissue rejection due to incompatibility is an experimental artifact masking the real function of MHC molecules: binding an antigen derived from self-proteins, or from pathogens, and bringing the antigen presentation to the cell surface for recognition by the appropriate T-cells. MHC molecules mediate the interactions of leukocytes, also called white blood cells (WBCs), with other leukocytes or with body cells. The MHC determines donor compatibility for organ transplant, as well as one's susceptibility to autoimmune diseases.
In a cell, protein molecules of the host's own phenotype or of other biologic entities are continually synthesized and degraded. Each MHC molecule on the cell surface displays a small peptide (a molecular fraction of a protein) called an epitope. The presented self-antigens prevent an organism's immune system from targeting its own cells. The presentation of pathogen-derived proteins results in the elimination of the infected cell by the immune system.
Diversity of an individual's self-antigen presentation, mediated by MHC self-antigens, is attained in at least three ways: (1) an organism's MHC repertoire is polygenic (via multiple, interacting genes); (2) MHC expression is codominant (from both sets of inherited alleles); (3) MHC gene variants are highly polymorphic (diversely varying from organism to organism within a species). Sexual selection has been observed in male mice making mate choices of females with different MHCs and thus demonstrating sexual selection. Also, at least for MHC I presentation, there has been evidence of antigenic peptide splicing, which can combine peptides from different proteins, vastly increasing antigen diversity.
Lloyd John Old (September 23, 1933 – November 28, 2011) was one of the founders and standard-bearers of the field of cancer immunology. When Old began his career in 1958, tumor immunology was in its infancy. Today, cancer immunotherapies are emerging as a significant advance in cancer therapy.Old's contributions to research established many of the principles and priorities of modern tumor immunology. In earlier work, he and his colleagues introduced Bacillus Calmette-Guérin (BCG) to tumor immunotherapy; discovered the first link between the major histocompatibility complex (MHC) and disease (leukemia); found the unexpected association between Epstein-Barr virus (EBV) and nasopharyngeal carcinoma; discovered Tumor necrosis factors (TNF); defined the concept of cell-surface differentiation antigens with the discovery of TL, Lyt (CD8), and a range of other mouse antigenic systems; discovered p53, independently with two other groups; and identified the tumor immunogenicity of heat shock proteins. Old is the author or co-author of more than 800 research publications. He was also a teacher helping young scientist as they began their career.
He held the William E. Snee Chair of Cancer Immunology at Memorial Sloan-Kettering Cancer Center (MSKCC), where he was director of the Ludwig Cancer Research New York Branch (then known as Ludwig Institute for Cancer Research, or LICR). He was also a trustee of the LICR Charitable Trust, and a trustee of the Virginia & D.K. Ludwig Fund for Cancer Research.6. From 1971 to 2011, he served as the founding scientific and medical director of the Cancer Research Institute (CRI), where from 2001 to 2011 he also served as director of the CRI/LICR Cancer Vaccine Collaborative (CVC), an international network dedicated to testing and optimizing therapeutic cancer vaccines. Old's previous appointments included chairman of the LICR board of directors (2006–2009), LICR scientific director (1988 to 2005), member of the Emeritus LICR Scientific Committee (1971–86), LICR chief executive officer (1995–2004), and associate director of research at MSKCC (1973–83).
Old served as a member of scientific advisory boards and committees including the Public Health Research Institute of the City of New York, the National Cancer Institute, and the American Association for Cancer Research. Old was also a member of the American Association for Cancer Research, New York Academy of Sciences, Reticuloendothelial Society, Society of Experimental Biology and Medicine, American Association for the Advancement of Science, American Association of Immunologists, National Academy of Sciences, the Academy of Cancer Immunology, and the American Academy of Arts and Sciences. He had also received honorary doctor of medicine degrees from Karolinska Institute, the University of Lausanne, and the University College London. He graduated from the University of California, Berkeley with a B.A. in biology and earned a medical degree from the University of California, San Francisco.
Old died November 28, 2011, in his New York City home, after several years battling advanced prostate cancer.