n newborns and the elderly, bacterial infection causes major lifethreatening illnesses, including pneumonia, meningitis and sepsis. The bacteria responsible (e.g. Haemophilus influenzae and Streptococcus pneumoniae) are typically surrounded by polysaccharide capsules. One important susceptibility factor for recurrent bacterial infection, which manifests itself at both extremes of life, is a deficit in anti-polysaccharide antibodies to encapsulated pathogens. At present, the molecular and cellular bases for this innate/acquired immunodeficiency are not understood. However, an important immunological advance potentially relevant to this problem is the CD1 system of antigen recognition 1,2 .
The CD1 system of antigen recognition
Human CD1a-d constitute a family of nonpolymorphic molecules. Although not encoded within the major histocompatibility complex (MHC), their association with β€ 2 -microglobulin relates them structurally to MHC class I proteins, with which they also share limited but significant sequence homology. CD1 molecules are expressed on immature thymocytes and professional antigen-presenting cells (APCs), including dermal dendritic cells (DCs), cytokine-activated macrophages and B cells 2-4 . These observations suggested a role for CD1 in antigen presentation, and formal proof has now emerged demonstrating presentation of mycobacterial nonpeptide antigens by CD1b and CD1c (Refs 5-9).
An important precedent for the hypothesis described here was the isolation of a T-cell receptor β£β€ Ο© CD4 Οͺ CD8 Οͺ double-negative (DN) T-cell line, LDN4, from a patient with leprosy 7 . This T-cell line responded to a nonpeptide antigen from Mycobacterium leprae in a CD1b-restricted manner as determined by its proliferation, interferon β₯ production and cytolytic activity. Most importantly, the nonpeptide antigen recognized by LDN4 was identified as lipoarabinomannan (LAM; Fig. 1). LAM comprises a mannose polymer substituted at one end with arabinan and at the other with palmitic and tuberculostearic acids. De-O-acylation of LAM by mild alkali hydrolysis totally abrogates T-cell responsiveness, indicating that the linkage of fatty acid to carbohydrate is important for antigen recognition and/or presentation 7 .