An organ system without a proper name

As every high-school graduate knows, animals are classified into two large groups ñ those that have vertebrae and those that do not. What every high-school graduate should also know (but probably doesnít) is that the vertebrates are further divided into jawless (Agnatha) and jawed (Gnathostomata). The jawed vertebrates are distinguished not only by the possession of jaws, but also by a suite of other characters, including an immune system based on the use of the ìholy trinityî or three sets of molecules ñ the major histocompatibility complex (MHC) molecules, the T-cell receptors (TCRs), and the B-cell receptors or immunoglobulins (BCRs or Igs; see Klein et al., 2000). The system is referred to as adaptive or acquired, but both designations are misleading and inaccurate; a term like anticipatory immune system (Klein, 1989) would have, perhaps, been more appropriate, but it did not take. Fortunately, the acronyms for all three names are the same ñ AIS. Immunologists originally believed that the AIS is present in both vertebrates and nonvertebrates (Cooper, 1976), but I have argued for some time (Klein, 1989, 1997) that the system is restricted to vertebrates and possibly to jawed vertebrates only. The first part of this proposition is now generally accepted; the second part is still debated, but this debate, too, is close to resolution. If we accept the holy trinity as the defining feature of the AIS, mounting evidence indicates that the agnathans lack the system, for the trinity appears to be present in all gnathostomes, but absent in jawless vertebrates. The most compelling evidence for the absence of the trinity in jawless vertebrates has been provided by recent studies in which cells resembling mammalian lymphocytes have been purified from lamprey organs and cDNAs obtained from the gene transcripts present in these cells have been sequenced (Mayer et al., 2002a; Uinuk-Ool et al., 2003 and unpublished data). By this approach, some 30,000 lamprey cDNA sequences have been collected and through them numerous genes expressed in the lymphocyte-like cells have been identified. However, no members of the trinity could be found in the collection. Although definitive evidence for the absence of the trinity will have to await the completion of the entire lamprey genome sequence, the cDNA sequences suggest strongly that MHC, TCR, and BCR genes as we know them from gnathostomes are absent in the lamprey and probably also in the hagfish. Assuming this to be the case, an inquiry into the nature of the agnathan immune system can be expected to yield valuable information about the transition from non-AIS to AIS at the time of divergence of jawless and jawed vertebrates.