e r o s , .d ea}ures #nmunology Today, Vol. 11, No 7 1990

Sandoz Prize: T-B collaboration

Jacques Miller Max Cooper The inaugura!SandozPrizeforlmmu- of the winners to the elucidation nology has been awarded to Drs Max of B-cell (Coopar) and T-cell (Miller) Cooper of the University of Alabama, biology. Birmingham, and Jacques Miller of Each has exerted a great influence the Walter and Eliza Hall Institute in on his chosen field. Jacques Miller's Melbourne. The prize, presented at achievements include the origina! the AAI meeting in New Orleans in demonstration of the ~-ole of the ti~y- June, recognizes the contributions mus in the development of immuno-

competence, seminal work on T-B cell cooperation and insights into the function of CD4 and CD8 in T-cell activation. Max Cooper and col- leagues were the first to establish that the immune system can be divided, developmentally and func- tionally, into B- and T-cell popu- lations. He has contributed substan- tially to the understanding of B-cell ontogeny, the mechanisms and treat- ments of B-cell immunodeficiencies and the processes governing the de- velopment of B-cell neoplasms.

The prize of $100 000 will hence- forth be awarded biennially, with the winners selected by a prestigious international jury. The aim of the prize is both to honour achievement in immunology and to encourage further research. The latter is re- flected in the use of the winnings: Jacques and Max will use 80% to fund further research.

Richard Gallagher Editor of Immunology Today.

Heat shock proteins: immunity and immunopathology ......

from Peter M. Lydyard and Willem van Eden

Much interest has been generated in heat shock proteins (hsps) since they were im- plicated as dominant antigens of infec- tious microorganisms and suggested to have a role in the development of adju- vant arthntis (AA) in rats. Advances in the understanding of the role of hsps in im- munity and immunopathology were re- cently discussed at a meeting held in Utrecht*, as part of the European Com- munity concerted action on immunopatho- genesis and irnmunotherapy of chronic art, hritis.

Heat shock proteins can be divided into four major families, with mem- bers of molecular mass of about 90kDa, 70kDa, 60kDa and 10- 30 kDa. Most of the discussion at the meeting revolved around the 60 kDa and 70 kDa family members (re-

*The mini-symposium on Heat Shock Pro- teins, Immunity and Immunopathology was held in Utrecht on 2 April 1990. 228

viewed by D. Young, London). Pro- karyotic hsps of these families share as much as 60% homology with mammalian forms at the amino acid level. They occur constitutively but can also be induced by a variety of stress conditions. !hey function as 'molecular chaperones' (J. Ellis, War- wick) which are defined as proteins that mediate corrc.ct folding of other proteins and, in so.me cases, their assembly into oligomeric structures.

A constitutive member of the hsp70 family is involved in anti- gen processing and presentation (S. Pierce, Evanstown). Using anti- immunoglobulin covalently coupled to cytochrome c and murine B cells as antigen-processing cells, it was shown that small peptides of the anti- gen can be detected intracellularly attached to a 72-74 kDa peptide- binding protein within minutes. Antibodies to this 72-74 kDa hsp blocked the T-cell recognition of cytochrome c. The hsp was localized

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to endosomal and surface mem- branes of macrophages and B cells, but was not found on T and natural killer (NK) cells. A fundamental role for this particular hsp70 could be to prevent total degradation of the pep- tide within endosomes and to carry the peptides to the surface for co- assembly with class II (and class I?) MHC molecules.

Immunity to heat shock proteins During infection, hsps are induced

in both microorganisms and host phagocytes. The dominant antigens of intracellular microorganisms are hsp65 and hsp70. Cloned 'autoreac- tive' T cells have been obtained from normal donors for human hsp65 and hsp70 (D. Young). Could such T cells damage 'stressed' cells? In fact, virally infected, gamma-interferon (IFN-~/)- or heat-treated macrophages were killed by T cells from M. leprae infected mice recognizing conserved epitopes of hsp65 (S. Kauffman, Ulm).

Previous studies have suggested a role for ~/~ T cells in mycobacterial disease. In vitro stimulation of blood T cells with M. tuberculosis extract in- creased ~/a T cell numbers (S. Kauff- man). However, this effect was not specific to mycobacteria. Further- more, precursor frequency, analysis showed that hsp65 was not the

1990, Elsevier Science PublishErs Ltd, UK. 0 i 67-4919/90/502.00