A functional genomic approach, based on systematic data gathering, was used to characterize a family of proteins containing a tripartite motif (TRIM). A total of 37 TRIM genes/proteins were studied, 21 of which were novel. The results demonstrate that TRIM proteins share a common function: by means of homo-multimerization they identify speci®c cell compartments.

An advanced variable selection procedure, called GOLPE, aimed at obtaining PLS regression models with the highest prediction ability is presented and illustrated with an application in 3D‐QSAR. Key steps in the procedure are a preliminary variable selection by means of a D‐optimal design in the loading space, and an iterative evaluation of the effects of individual variables on the model predictivity based on the validation of a number of reduced models, on variables combinations selected according to a FFD strategy. The procedure is successfully applied to a real 3D‐QSAR case study: the results obtained by GOLPE are compared with those obtained by CoMFA and found to be in good agreement in terms of variable importance, but with a much higher prediction ability. Accordingly, the results encourage to think that it might be used within the CoMFA framework in the place of the present PLS version there, or in CoMFA‐like studies on the structures generated by GRID probes.

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SummaryPresentation of antigenic peptides by human leukocyte antigen class I molecules is dependent on peptide transport into the endoplasmic reticulum by the transporters associated with antigen processing (TAP) (Germain, R. N. 1994. Cell. 76:287-299) . This translocation step is currently regarded as permissive for all peptides with COON-terminal residues capable of binding to HLA class I molecules (Momburg, F., J . Roelse, J. C. Howard, G. W. Butcher, G . J. Hammerling, and J. J. Neefjes . 1994. Nature (Loud .) . 367 :648-651) . In this report, we show that the human transporter selects peptides according to a binding motif based on the strong effects on peptide affinity of the three NHZ-terminal positions and the COOH-terminal residues . TAP favors strongly hydrophobic residues in position 3 (P3) and hydrophobic or charged residues in P2, whereas aromatic or acidic residues in P1, as well as Pro in P1 and P2, have strong deleterious effects . Selection of naturally presented peptides by the transporter is suggested by their higher average affinity for TAP, as compared to nonselected peptides . The TAP preferences in the three NHZ-terminal positions correspond to those ofthe vast majority of human leukocyte antigen class I alleles, but they represent an obstacle for peptide supply to some alleles, e.g., the B7-like group . We propose that peptides binding to these alleles, and in general, peptides with TAP affinities below a certain threshold, may be transported as extended precursors .M HC class I proteins present short breakdown products of predominantly cytosolic proteins on the cell surface to cytotoxic T lymphocytes (reviewed in reference 1) . Most of these peptides are supplied to newly assembling MHC class I proteins by the heteromeric transporter associated with antigen processing (TAP)'/TAP2' transporter complex residing in the membrane of the endoplasmic reticulum (ER) . Peptide transport by TAP can be studied using iodinated peptide substrates whose accumulation in the ER is followed grace to an integrated acceptor sequence for ER-specific glycosylation (2-4). As an alternative strategy for the study of TAP function, we recently overexpressed the human TAP complex in the insect cell/baculovirus system . In this system, peptide transport by TAP, as well as direct binding of peptide substrate to the transporter complex, can be measured (5, 6).'Abbreviations used in this paper: (3 2 m, R2-rnicroglobulin ; DTT, dithiothreitol; ER, endoplasmic reticulum ; TAP, transporter associated with antigen processing.Although the functional consequences of a polymorphism in the rat TAP2 gene clearly demonstrate that TAP selection can modify the spectrum of peptides presented by MHC class I molecules (7), it is not clear whether the human or murine transporters contribute to selection of class I-presented epitopes. Apart from a preference for peptides with a length of 8-16 residues (5,8,9), the only selectivity of the transporters known so far concerns the COOH-terminal residue. In this position, the human TAP com...

SUMMARYA procedure called GOLPE is suggested in order to detect those variables which increase the predictivity of PLS models. The procedure is based on evaluating the predictive power of a number of PLS models built by different combinations of variables selected according to a factorial design strategy. Examples are given of the efficiency of this variable selection procedure, which shows how these predictive PLS models are better than those obtained by all variables and better than the corresponding ordinary regression models.