ABSTRACT

The last decade witnessed an explosion in information concerning the mechanisms underlying the host’s immune response to invading microorganisms, as well as during pathological conditions such as autoimmune diseases and cancer. This was largely a result of impressive technological advances, which include: (1) engineering of a multitude of single and multiple gene-knockout and transgenic animals (and more recently, “conditional knockout” and “knockin“mutants); (2) the ability to track specific T cells by using fluorochrome-labeled peptide-major histocompatibility complex (MHC) tetramers; (3) sophisticated multicolor and flow cytometric sorting techniques that allow the identification and functional characterization of cell sub-populations based on the concomitant expression of multiple surface and intracellular molecules; (4) the availability of many cytokines, chemokines, and other immunoregulatory molecules produced by recombinant techniques; (5) gene expression profiling using DNA microarrays that allows one to simultaneously determine the expression of thousands of individuals genes in response to infection; and (6) the advent of proteomics (i.e., the large-scale analysis of proteins and their interactions). Moreover, the disclosure of the DNA sequence of entire genomes, not only of humans, but also from an ever-increasing number of other eukaryotic (e.g., yeasts, worm, and fly) and prokaryotic (currently over 20) organisms, is allowing the identification of large numbers of potential novel target antigens (Ag) for vaccine development.